Biomedical subjects
Publications and source records attributed to C Colombo.
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3-Hydroxy-3-methylglutaric acid (HMGA) is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) and strongly reduces cholesterol biosynthesis both in vitro and in vivo. Since the effects of this compound on biliary lipid composition are hitherto unknown, we have investigated whether it prevents dietary cholesterol induction of saturated bile in the hamster. Female Golden Syrian hamsters have been divided into four groups and treated for 10 weeks as follows: I) Standard diet, containing 0.8 mg cholesterol/g food; II) Standard diet plus HMGA (100 mg/kg b.w./day per os); III) Lithogenic diet containing 2.4 mg cholesterol/g food; IV) Lithogenic diet plus HMGA as above. The results indicate that HMGA is effective in reducing both bile cholesterol supersaturation and hypercholesterolemia. Inhibition of hepatic cholesterogenesis at the level of mevalonate synthesis by HMGCoAR and reduction of intestinal cholesterol absorption may be responsible for these effects.
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An experimental model for the study of platelet-vessel wall interactions has been developed, based on perfusion of rat platelet rich plasma (PRP) through isolated rat aortas. In the perfused PRP, platelet aggregation was inhibited and levels of 6 Keto PGF1 alpha and cAMP were elevated over the values found in non perfused PRP. When PPP or buffer were perfused through the isolated artery, elevations of 6 Keto PGF1 alpha levels in the perfusate were smaller (in perfused PPP) or of shorter duration (in both perfused PPP and buffer). The presence of platelets in the perfusion fluid thus enhanced the formation of Prostacyclin by the arterial wall. Levels of 6 Keto PGF1 alpha in PRP obtained from aspirin-treated animals and in PRP from normal animals, both perfused through normal aortas, were the same, and also levels of the above metabolite in normal PRP perfused through aortas of aspirin-treated animals did not differ from those found in non perfused PRP. It is concluded, from these data, that PRP does not stimulate PGI2 formation in perfused aortas by providing cyclic endoperoxides. The experimental model developed allows the study of interactions between normal platelets and aortas from experimentally treated animals or viceversa.
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Semisynthetic diets containing 8% by weight of either corn oil or butter were fed to male New Zealand rabbits for three weeks. The plasma cholesterol values were determined, the threshold concentrations for aggregation of platelet rich plasmas were measured for collagen and Na arachidonate, and the conversion of 14C arachidonic acid to thromboxane B2 and hydroxy fatty acids (HETE and HHT) at 10, 20 and 40 microM substrate concentrations were studied. The thresholds for arachidonate induced aggregation were lower and the amplitudes of collagen induced aggregations were greater in the butter fed than in the corn oil fed rabbits. Conversions of arachidonic acid to thromboxane B2 but not to hydroxy fatty acids were greater in the butter fed rabbits at 10 and 20 microM substrate. The observed changes were accompanied by only slight modifications of plasma cholesterol levels.
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Emphysema was induced in rats by chronic exposure to a papain aerosol according to established methods. The emphysematous changes were evaluated by previously described histological and biochemical parameters and by a new method employing infiltration of the lungs with vinyl acetate to make casts of the air spaces of the pulmonary tree. The weights and gross and microscopic appearance of the casts demonstrated the emphysematous changes in lungs of the papain-treated rats. Vinyl acetate casting may offer a new and useful tool in evaluating experimental induction of emphysema in rats.
Chronic exposure of rats to 10% aerosols of papain or trypsin resulted in marked increases in lung weights and lung beta-glucuronidase and arylsulfatase activities. Destruction of alveolar walls was demonstrated microscopically as a decrease in the number of air spaces touching a line of known length. The pregnenes, progesterone and medroxyprogesterone acetate, but not the 19-nortestosterone derivative norethindrone, partially prevented the papain-induced breakdown of alveolar septa and elevation of beta-glucuronidase. The steroidal anti-inflammatory agent, paramethasone, completely inhibited the rise in lung weight and beta-glucuronidase activity, but did not prevent destruction of alveolar walls. The non-steroidal anti-inflammatory agent, indomethacin, afforded little or no protection. Limited prophylaxis against both histological and enzymatic changes was observed in rats treated with the anti-metabolite, cyclophosphamide, and the proteolytic enzyme inhibitor, aprotinin. The various lung abnormalities resulting from papain inhalation may thus be individually influenced by specific pharmacologic agents.
Osmotic release of beta-glucuronidase from polymorphonuclear leukocyte lysosomes is inhibited by catecholamines and adenosine 3',5'-monophosphate, and accelerated by cholinergic agents and guanosine 3',5'-monophosphate. These actions are specific for the sympathetic and parasympathetic neurotransmitters and for the two cyclic nucleotides, as phenylephrine, tyramine, choline, adenosine 5'-monophosphate and guanosine 5'-monophosphate do not inodify lysosomal enzyme release.
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