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M Orellana

Publications and source records attributed to M Orellana.

34 records · Page 2Linked to original sources
PubMed1988

Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism.

A new generation of heteroatom analogs of arachidonic acid are documented as powerful and selective inhibitors of the cytochrome P-450-dependent arachidonic acid oxygenase reaction (IC50, 5-10 microM) with little effect on either cyclooxygenase or soybean lipoxidase at 100 microM. The imidazole derivatives, ketoconazole and clotrimazole, are potent and selective inhibitors of the arachidonic acid epoxygenase and lipoxidase-like activities of phenobarbital-induced rat liver microsomal fractions (IC50, 2.0 and 0.3 microM, respectively). In contrast, the w/w-1 oxygenase activity of ciprofibrate-induced microsomal fractions was relatively resistant to inhibition by these compounds (IC50, 50 and 25 microM for ketoconazole and clotrimazole, respectively). Nordihydroguaiaretic acid (NDGA), eicosatetraynoic acid (ETYA), and indomethacin, extensively utilized inhibitors of the cyclooxygenase and lipoxygenase branches of the arachidonate cascade, also inhibit cytochrome P-450-dependent arachidonic acid metabolism. In decreasing order of potency, they were NDGA, ETYA, and indomethacin (IC50, 15, 40, and 70 microM, respectively).

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1988

Nutrition-related alterations in liver microsomal testosterone hydroxylases.

The oxidation products of testosterone formed by liver microsomes from normal-fed and protein-energy malnourished male rats have been analysed by HPLC. Microsomes from normal-fed rats oxidized testosterone at a rate of 4.52 nmol/min/mg protein. The major products formed were: 6 beta-, 7 alpha- and 16-alpha-hydroxytestosterone; these three metabolites represented 65% of the total testosterone metabolism. Microsomes from protein-energy malnourished rats oxidized testosterone at a reduced rate of 2.03 nmol/min/mg protein. The major product formed was 7 alpha-hydroxytestosterone, which accounted for 43% of total testosterone oxidation. Microsomes from protein-energy malnourished rats showed a CO-reduced cytochrome P-450 spectra with a maxima at 452 nm, and a 38% decrease in the total content of cytochrome P-450. Some testosterone hydroxylases were drastically affected by protein-energy malnutrition but others, such as 7 alpha-hydroxylase, remained unchanged. The present results suggest that nutritional status can modify the relative amounts of individual cytochrome P-450 isozymes, thus explaining the observed changes in several testosterone hydroxylases. Protein-energy malnutrition seems to be an excellent tool with which to obtain a microsomal fraction containing predominantly P-450 isozymes, which are probably involved in key mono-oxygenations of physiological substrates.

Animal Nutritional Physiological Phenomena↗
PubMed1981

Epidemiology of gastric cancer in Chile: I - Case-control study.

The results of a case-control study of stomach cancer carried out with the collaboration of 7 participating hospitals in Santiago, Chile are reported. Patients attending gastroscopy clinics were interviewed before or after gastroscopy. The diagnosis was unknown to either the patient or the interviewer at the time of interview. 360 stomach cancer cases were subsequently matched to non-cancer patients selected from the pool interviewed at the same time as the cases. Study findings show: 1) longer-term residence in high-risk areas in early life by cases than controls; 2) an association between stomach cancer and a prior occupation in agriculture. In a subgroup of 98 cases for whom histologic classification was available, the association with residence in early life in a high-risk area was seen only for cases with intestinal-type stomach cancer.

Adult↗
PubMed1981

Epidemiology of gastric cancer in Chile: II - Nitrate exposures and stomach cancer frequency.

Nitrate levels in urine and nitrite levels in saliva were determined in school children 11-13 years of age in 2 areas of high stomach cancer mortality located in central Chile and in 2 areas of low stomach cancer mortality located at the extremes of Chile. Levels of both nitrates and nitrites were concurrently determined in selected vegetables obtained in these 4 study areas. Levels of nitrates were significantly higher in the urine of schoolchildren and in vegetables obtained from the northern low-risk area. Levels of nitrites were similar in saliva specimens from all 4 areas, but levels in vegetables were inconsistent. These results are apparently incompatible with the hypothesis of a high nitrate intake in areas of high stomach cancer incidence compared to areas of low incidence. This paradoxical finding suggests that cofactors may be involved in the pathopoiesis of stomach cancer that promote or inhibit the transformation of dietary nitrates to nitrosamines. The soil in the high-risk areas is primarily of volcanic origin, which is reported to be low in levels of selenium. On the other hand, residents of Antofagasta, the northern low-risk area, are known to be exposed to high levels of arsenic. It is possible that the diet of residents of the high incidence area which may be deficient in selenium may enhance promotion of nitrates to nitrosamines as has been reported in the literature, or conversely, that high levels of arsenic or other factors in the diet of individuals in Antofagasta may play a protective role. Other factors may be responsible for the low rate observed in the southern low-risk area.

Adolescent↗
PubMedDate not supplied

Renal effects of experimental obstructive jaundice: morphological and functional assessment.

BACKGROUND: The pathophysiology of renal impairments occurring in obstructive jaundice has been extensively studied, but the underlying mechanism of these derangements remains unclear. The aim of the present study was to investigate the time-related morphological and functional changes occurring in the kidneys of rats undergoing obstructive jaundice. METHODS: Histological examination, renal function assessment and determination of (Na + K)-ATPase activity were performed in the kidneys of rats 7, 14, and 21 days following bile duct ligation (BDL) or sham operation (sham). RESULTS: Glomerular filtration rate was unaffected by BDL throughout the period of the study. Tubular effects occurred at days 7 and 14, being more marked at day 7, and consisted of an increase of about twice in the fractional excretion of sodium and chloride, paralleled by a decreased proximal and distal tubular reabsorption of sodium of about 50 and 40%, respectively. Natriuresis was consistent with augmentation of osmolar clearance but it was not associated with changes in the activity of renal (Na+ + K+)-ATPase. The ability to dilute urine was impaired at days 14 and 21 after BDL. Additionally, these effects were accompanied by decreased tubulointerstitial fibrosis and vasodilation of inner medullary capillaries. At day 21, the parameters of tubular function in BDL and sham groups were not significantly different. CONCLUSIONS: These data support the view that raised natriuresis taking place in the initial 2 weeks following BDL is due mainly to tubular effects. The contribution of hemodynamic, paracrine and humoral mediators is discussed.

Animals↗