Atherosclerosis described

As described in the previous section, bile acids have evolved over the last years from regulators of bile acid homeostasis to general metabolic integrators. It is therefore not too surprizing that a number of bile acid-activated signaling pathways have become attractive targets for the treatment of gallstones and other metabolic diseases, such as obesity, type 2 diabetes, hyperlipidemia, and atherosclerosis. 

A recent patent application from Roche [352] described a 2-amino-benzothiazole series. Roche claimed that compound (605) exhibited an IC50 value of 0.73 uM at CBi, and showed in excess of 10-fold selectivity over the CB2 receptor. The compounds were described as being of potential use in the treatment of a range of diseases, including CNS and psychiatric disorders, type-2 diabetes, gastrointestinal diseases, cardiovascular disorders, infertility disorders, inflammation, cancer, atherosclerosis, cerebral vascular incidents and cranial trauma. 

JLompre I would like to present some of our results describing the changes that occur to cells in culture. My concern is primarily with the organization of the SR when vascular smooth muscle cells proliferate in culture. This is of interest because of the importance of smooth muscle cell proliferation in atherosclerosis and restenosis. Freshly dissociated cells or those that have been cultured for just one... 

Epileptiform fits associated with degenerative changes in the myelin sheath of peripheral nerves and spinal cord occur in B6-deficient animals. Lesions in the arteries, resembling those of human atherosclerosis, have been observed in Be-deficient monkeys. Recently, a state of Be deficiency in human infants, characterized by loss of ability to convert tryptophan to nicotinic acid, by impaired growth, convulsions, and hypochromic anemia, has been described, following omission of vitamin B6 from the diet. 

Several peptides possessing antihypertensive effect proved to play a promising role in regnlating vascnlar fnnctions as described in the past researches. The present chapter is aimed to offer an overview of a new functionality of small peptides in preventing hypertension and vessel dysfunctions including atherosclerosis. 

Autonomic nerves can regulate coronary arteriolar tone. Acetylcholine released from postganglionic parasympathetic nerves relaxes coronary arteriolar smooth muscle via the NO/cGMP pathway in humans as described above. Damage to the endothelium, as occurs with atherosclerosis, eliminates this action, and acetylcholine is able to contract arterial smooth muscle and produce vasoconstriction. Skeletal muscle receives sympathetic cholinergic vasodilator nerves, but the view that acetylcholine caused vasodilation in this vascular bed has not been verified experimentally. Moreover, NO, rather than acetylcholine, may be released from neurons. However, this vascular bed responds to exogenous choline esters because of the presence of M3 receptors on endothelial and smooth muscle cells. 

As described above, halichlorine was shown to inhibit LPS-induced events in BAECs, including adhesion-molecule expression, adherence of monocytes, and NF- activation. Thus, halichlorine is thought to be an attractive candidate for the adjunctive therapy of diseases such as atherosclerosis. 

Miwa and Yamamoto (31) described a simple and rapid method with high accuracy and reliability for the determination of C8 0-C22 6 fatty acids, which occur in esterified forms in dietary fats and oils and in living cells [the biological effects of routinely consumed fats and oils are of wide interest because of their impact on human health and nutrition (28,29), in particular, the ratio of cu-3 polyunsaturated fatty acid to w-6 polyunsaturated fatty acids (w-3/cu-6) seems to be associated with atherosclerosis and breast and colon cancers (30)]. They report improved separation of 29 saturated and mono- and polyunsaturated fatty acids (C8-C22), including cis-trans isomers and double-bond positional isomers, as hydrazides formed by direct derivatization with 2-nitrophenylhydrazine hydrochloride (2-NPH HC1) of saponified samples without extraction. The column consisted of a J sphere ODS-M 80 column (particle size 4 /xm, 250 X 4.6-mm ID), packed closely with spherical silica encapsulated to reach a carbon content of about 14% with end-capped octadecyl-bonded-spherical silica (ODS), maintained at 50°C. The solvent system was acetonitrile-water (86 14, v/v) maintained at pH 4-5 by adding 0.1 M hydrochloric acid with a flow rate of 2.0 ml/min. Separation was performed within only 22 min by a simple isocratic elution (Fig. 6). The resolution of double-bond positional isomers, such as y-linolenic ( >-6) and a-linolenic acid ( >-3) hydrazides and w-9, >-12, and >-15 eicosenoic acid hydrazides was achieved by use of this column. 

Angiotensin II is an octapeptide, which was initially described as a potent vasoconstrictor agent. However, its functions have since been expanded to include regulation of cell growth, inflammation, electrolyte and water balance, hormone secretion, sympathetic nervous system activity, differentiation, and apoptosis. The discovery that it is produced both systemically and locally was instrumental in establishing a pivotal role for the peptide in several disease states, including hypertension, coronary heart disease, myocarditis, congestive heart failure, atherosclerosis, and nephrosclerosis. 

Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice were described by Paigen et al. (1990). 

Beere et al. (1992) described experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey by a cholesterol-enriched diet. 

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