Unusual dynamics of extinction in a simple ecological model.

Studies on natural populations and harvesting biological resources have led to the view, commonly held, that (i) populations exhibiting chaotic oscillations run a high risk of extinction; and (ii) a decrease in emigration/exploitation may reduce the risk of extinction. Here we describe a simple ecological model with emigration/depletion that shows behavior in contrast to this. This model displays unusual dynamics of extinction and survival, where populations growing beyond a critical rate can persist within a band of high depletion rates, whereas extinction occurs for lower depletion rates. Though prior to extinction at lower depletion rates the population exhibits chaotic dynamics with large amplitudes of variation and very low minima, at higher depletion rates the population persists at chaos but with reduced variation and increased minima. For still higher values, within the band of persistence, the dynamics show period reversal leading to stability. These results illustrate that chaos does not necessarily lead to population extinction. In addition, the persistence of populations at high depletion rates has important implications in the considerations of strategies for the management of biological resources.     

Cationic peptides neutralize Ox-LDL,prevent its uptake by macrophages,and attenuate inflammatory response

Objective

Apolipoprotein A1 (ApoA1) and apolipoprotein E (ApoE) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins, inhibit their uptake and inflammation by macrophages.

Methods and results

5F-mimetic peptide of ApoA1, LL27 derived from the anti-microbial peptide hCAP, and a human glycodelin derived peptide were commercially synthesized. We noted that these three distinct cationic lysine-rich peptides, two of which were unrelated to any known apolipoproteins, inhibited copper-mediated oxidation of lipoproteins and reduced lipid peroxides in a lysine dependent manner. The peptides also retarded the electrophoretic mobility of previously oxidized LDL and acetylated LDL by virtue of their net positive charge. Pre-incubation of peptides with modified lipoproteins reduced the uptake of the latter by macrophages, thus preventing the formation of foam cells. The cationic peptides inhibited oxidized LDL (Ox-LDL)-induced inflammatory response both in vitro and in vivo.

Conclusion

Based on these results, we suggest that in addition to the well known mimetic peptides, other suitable cationic peptides may be of use for controlling Ox-LDL mediated inflammation and atherosclerotic progression.     

In vivo inhibition of foam cell development by probucol in Watanabe rabbits

Previous studies from this laboratory have shown that oxidative modification of low-density lipoprotein (LDL) causes it to be recognized by the scavenger receptor of the macrophage. Consequently, the rate of degradation of oxidized LDL by macrophages can be 3 to 10 times that of native LDL. Antioxidants, such as probucol, are highly effective in preventing the oxidative modification of LDL. Our recent studies show that probucol treatment of LDL receptor-deficient Watanabe heritable hyperlipidemic (WHHL) rabbits selectively inhibits the degradation of LDL in fatty streak lesions (which are rich in macrophage-derived foam cells) without inhibiting degradation in nonlesioned areas (where degradation is predominantly in smooth muscle cells, which do not express the scavenger receptor). Furthermore, the rate of progression of lesions in probucol-treated animals was significantly slower than in a lovastatin-treated group maintained at equal total plasma cholesterol levels. These results strongly suggest that probucol, through an antioxidant activity not necessarily related to its ability to lower plasma cholesterol levels, can slow the progression of the foam-cell-rich fatty streak lesion of atherosclerosis.     

Oxygen radicals, antioxidants, and lipid peroxidation

Reactive oxygen species derived from molecular oxygen are highly reactive metabolites. These species can be generated by cellular or acellular mechanisms. They react with all biological molecules such as protein, lipid, and carbohydrates. The reaction of these species with lipids, called lipid peroxidation, is a very well-studied phenomenon. Compounds, which scavenge these molecules, are called antioxidants. The disruption of the delicate balance between pro- and antioxidants has been implicated in the pathophysiology of many chronic diseases such as, for example, atherosclerosis. This article presents an introduction to what reactive oxygen species are and their reactions with various metabolites. It deals with lipid peroxidation in detail and with methods for measuring lipid peroxidation. This article also outlines the importance of these species in the pathology of various gynecological diseases.     

Conformation of O6-alkylguanosines: molecular mechanism of mutagenesis

The O⁶-alkylation of guanine residues in DNA treated with alkylatingagents induce mutations due to mis-pairing resulting from thedeprotonation of N1. In addition to the deprotonation of N1,the conformation of the O⁶-alkyl group with respect to N7 ofguanine is very important. Here, we present X-ray crystallographicevidence that shows that the methyl group in O⁶-methylguanosinehas a preference for the distal conformation, blocking the Watson-Cricksites. This distal conformation persists in the solid statefor several analogs of O⁶-alkylguanosine also. This preferredconformation agrees with the result that poly(O⁶-methyl GMP)does not form any stable complex with poly(U). However, themispairing of O⁶-methylguanine with thymine and the resultantGA transition is known from in vitro studies. The above twoopposite results strongly indicate that the conformation ofthe O⁶-alkyl group and the base pairing properties of O⁶-alkylguanineat the monomer and polymer levels must be different from thesituation when the modified base is embedded with a small frequencyin a duplex. It is interesting to note that the sterical blockingof the Watson-Crick site at the monomer level and the alteredbase pairing properties when present as occasional bases ina duplex emerge as a common property for several mutagenic baseslike O⁶-alkylguanmes, O⁴ -methyluracil and N⁴-hydroxycytosine.     

Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal carcinoma in rats

Colorectal cancer, a common cause of cancer related deaths in both sexes in western population is often due to persistent oxidative stress leading to DNA damage. Antioxidants scavenge free radicals and inhibit neoplastic process. Kaempferol, a flavonol widely distributed in tea, broccoli, grape fruit, brussel sprouts and apple and is claimed to have chemopreventive action in colon cancer. The aim of our study was to evaluate the effect of kaempferol on tissue lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal cancer in male wistar rats and to compare its efficacy with irinotecan. Experimental colon cancer induced by 1,2-dimethyl hydrazine in rats mimic human colon cancer and therefore is an ideal model for chemoprevention studies. The rats were divided into six groups. Group 1 served as control. Group 2 received 1,2-dimethyl hydrazine (20 mg/kg body weight) subcutaneously once a week for four weeks. Group 3 received irinotecan (100 mg/kg body weight) intravenously once a week for four weeks with 1,2-dimethyl hydrazine. Groups 4 to 6 were given a daily oral dose of 50, 100, 200 mg/kg body weight of kaempferol with 1,2-dimethyl hydrazine. The total study period was 16 weeks. Kaempferol supplementation lowered 1,2-dimethyl hydrazine induced erythrocyte lysate and liver thiobarbituric acid reactive substances level and rejuvenated anti oxidant enzymes catalase, super oxide dismutase and glutathione peroxidase. The recovery of enzyme status was maximum at the dose of 200 mg/kg body weight and was comparable to irinotecan. Our study reveals that kaempferol could be safely used as a chemopreventive agent in colorectal cancer.