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J L Alfonso

Publications and source records attributed to J L Alfonso.

7 recordsLinked to original sources
PubMed2001

Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture of very long chain saturated fatty acids.

The present study was undertaken to investigate the effects of D003, a mixture of very long chain saturated fatty acids isolated and purified from sugar cane wax, on cholesterol biosynthesis in cultured fibroblasts. Cholesterol biosynthesis is regulated through feedback regulation of at least two sequentially acting enzymes, 3-hydroxy-3-methyl coenzyme A (HMG-CoA) synthase and reductase. They are up-regulated when sterol levels fall and down-regulated when sterol levels rise. The exposure of cultured fibroblasts to a lipid-depleted medium (LDM) and D003 (0.05-50 microg ml(-1)) for 12 h inhibited, in a dose-dependent manner, cholesterol biosynthesis from 14C-labelled acetate (33-68%). The addition of D003 at concentrations inhibiting cholesterol biosynthesis from labelled acetate significantly decreased incorporation of radioactivity from 3H2O into sterols, but not from 14C-mevalonate. These data indicate that D003 inhibits cholesterol biosynthesis by interfering with early steps of cholesterol biosynthetic pathway. We reasoned that D003 acts directly on HMG-CoA reductase, the main regulatory enzyme of cholesterol biosynthetic pathway. However, when enzyme activity was measured in cell extracts in the presence of various concentrations of D003 (0.5-50 microg ml(-1)), reductase activity was not inhibited. Thus, there was no evidence for a competitive or non-competitive inhibition of enzyme activity by D003. Treatment with D003 significantly suppressed (68%) the enzyme up-regulation when cells were cultured in LDM, which suggests a depression of de novo synthesis of HMG-CoA reductase and/or a stimulation of its degradation. However, since the suppressive action of D003 on cholesterol biosynthesis was observed in metabolic conditions under which synthase up-regulation was also enhanced, we cannot rule out a possible effect of D003 on HMG-CoA synthase. Thus, further studies are needed to clarify the precise mechanism of the inhibitory effect of D003 on cholesterol biosynthesis.

Animals↗
PubMed1996

The effectiveness of health systems in influencing avoidable mortality: a study in Valencia, Spain, 1975-90.

OBJECTIVES: To measure variations in the Holland and Charlton classifications of avoidable death causes and to estimate the effect of the Spanish national health system on avoidable mortality. DESIGN: Mortality in the Valencian Community was assessed between 1975 and 1990. The classifications of Holland and Charlton, used to assess avoidable causes of death, were compared. Holland's classification was then used to divide avoidable mortality into two groups--medical care indicators (MCI), which show the effectiveness of health care, and national health policy indicators (NHPI), which show the status of primary prevention. Comparisons were made with rates, group rates, and population rates. Trends and indices were also studied. SETTING: Valencia, Spain, 1975-90. RESULTS: During the study period, avoidable morality (only assessed by MCI) fell 63%, whereas the remainder of the mortality (non-MCI causes, that is all the non-avoidable causes together with the NHPI group) fell by 17%. If it is assumed that the mortality due to non-MCI causes indicates the overall effect of the environmental, social, nutritional, and genetic influences, then the difference between this and the MCI group would take us nearer the actual effect of the intervention of the health system. CONCLUSIONS: It is concluded that in this community, the health system has been responsible for approximately 47% of the total reduction in mortality from avoidable causes in the period studied.

Adolescent↗
PubMed1992

Inguinal hernia and certain risk factors.

There are several studies on inguinal hernias that give some clues about the association between this type of hernia and certain risk factors. This association was suspected long ago but had not been demonstrated. The present study tries to correlate the origin of inguinal hernias and the physical effort of the subjects in accordance with their work activity. The results of this study show that physical effort, as a risk factor, is closely related to the appearance of inguinal hernias. A person whose work involves lifting or other strenuous exertion has a higher risk than those whose jobs are less strenuous (p less than 0.05). This conclusion was reached after taking into account not only the weight lifted but also the number of years in this activity.

Alcohol Drinking↗
PubMed1989

[Cancer of the testis: risk factors and evolution of mortality in Spain (1951-1983)].

Herein we report the results of a study on the mortality trends of testicular cancer in Spain from 1951-1983. The study showed that following a long period of increased mortality, overall mortality rates for all age groups have dropped in recent years. However, the mortality rate has increased for the young and middle-aged males and has dropped for the older age groups. A similar finding has been observed for other countries such as the United States. We have attempted to interpret these changes based on the risk factors for this type of cancer.

Age Factors↗
PubMedDate not supplied

Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts.

BACKGROUND: Cholesterol biosynthesis is strictly controlled by 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase. METHODS: Transfer of cultured fibroblasts to a lipid-depleted medium (LDM) up-regulates the enzyme levels. This, in turn, is followed by an accelerated biosynthesis of cholesterol. RESULTS: Exposure of Vero fibroblasts to LDM and policosanol (0.5-50 microg/mL), a new cholesterol-lowering drug purified from sugarcane (Saccharum officinarum L.) wax, decreased in a dose-dependent manner cholesterol biosynthesis from [14C]-acetate and 3H-water, but not from [14C]-mevalonate. CONCLUSIONS: This suggests an effect on HMG-CoA reductase, the rate-controlling enzyme in cholesterol biosynthesis. When enzyme activity was measured in the presence of various concentrations of policosanol (0.5-50 microg/mL), reductase was not suppressed. Therefore, there was no evidence for a competitive or noncompetitive inhibition of enzyme activity. However, after treatment of intact cells with policosanol (50 microg/mL) in the presence of LDM, a suppressive effect on enzyme activity was observed, suggesting a modulatory effect of policosanol on reductase activity. The previous inhibition of enzyme up-regulation by policosanol suggests to date a depression of de novo synthesis of HMG-CoA reductase and/or stimulation of its degradation. However, the exact mechanism by which policosanol inhibits the activity of HMG-CoA reductase still remains unclear. Further studies are needed to clarify the precise mechanism of its inhibitory action on cholesterol biosynthesis.

Animals↗
PubMedDate not supplied

[Multihospital systems].

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Multi-Institutional Systems↗