PubMed HealthSearch

Biomedical subjects

E Herrera

Publications and source records attributed to E Herrera.

At least 19 recordsLinked to original sources

Effect of streptozotocin diabetes on polysomal aggregation and protein synthesis rate in the liver of pregnant rats and their offspring.

To study the effect of diabetes on hepatic protein synthesis and polysomal aggregation in pregnant rats, female rats were treated with streptozotocin prior to conception. Some animals were mated, and studied at day 20 of pregnancy, whereas, others were studied in parallel under non pregnant conditions. The protein synthesis rate measured with an "in vitro" cell-free system was higher in pregnant than in virgin control rats. It decreased with diabetes in both groups, although values remained higher in diabetic pregnant rats than in the virgin animals. The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they showed a higher protein synthesis rate than either their respective mothers or virgin rats. Liver RNA concentration was higher in control and diabetic, pregnant rats than in virgin rats, and the effect of diabetes decreasing this parameter was only significant for pregnant rats. Liver RNA concentration in fetuses was lower than in their mothers, and did not differ between control and diabetic animals. The decreased protein synthesis found in diabetic animals was accompanied by disaggregation of heavy polysomes into lighter species, indicating an impairment in peptide-chain initiation.

Animals

Effect of etofibrate on bile production in the normolipidemic rat.

1. The effect of etofibrate, the ethandiol-1,2 diester of nicotinic and clofibric acids on bile production was studied in male rats that received a daily dose of 300 mg of etofibrate/kg body weight by stomach tube for 10 days and were compared with control rats receiving the medium. 2. The bile duct was cannulated, animals were intravenously given 1 microCi (4-14C)-cholesterol/100 b.w. and bile was collected at different intervals for a total of 4 hr. 3. Etofibrate treatment decreased plasma cholesterol and triglyceride concentrations and increased the bile flow. The cummulative amount of both bile volume and total bile radioactivity secreted increased linearly in all the animals; the respective slopes being higher in etofibrate treated rats than in controls. 4. The main labelled component found in the bile was always bile acids rather than cholesterol and the proportion of each of these compounds was similar in both groups. Neither was any difference between the groups found in the concentration of bile acids, cholesterol and phospholipids nor in the cholesterol/(bile+phospholipid) ratio. 5. Besides other factors, the present results indicate that an increase in bile flow and biliary cholesterol excretion in its free form and after its conversion into bile acids should contribute to the hypocholesterolemic effect of etofibrate.

Animals

Sperm migration through the female genital tract of the New World monkey Cebus apella.

This study was designed to characterize sperm migration in the female genital tract of Cebus apella. Forty-eight cycles of eighteen females mated during the periovulatory period were studied. Eggs were searched for and spermatozoa were counted in segmental flushings of the genital tract performed in situ 1-7 h, 19-31 h, or 45-56 h after coitus. Of 14 eggs recovered, 8 were fertilized, thus assuring a reasonable normality of prefertilization phenomena in both males and females. A downward gradient of several orders of magnitude in sperm numbers was recognized from cervix to ampulla, particularly over the first interval. The population in the cervix and uterus decreased progressively between the first and last interval. Spermatozoa were recovered from the ampulla as early as 1 h after mating. Different trends were observed in the isthmus and ampulla. From the first to the last interval, sperm numbers decreased in the ampulla, but not in the isthmus. The number of spermatozoa recovered from the ampulla of the ovulatory side 1-31 h postcoitum was higher in postovulatory than in preovulatory monkeys, while in the nonovulatory side, recovery was similar in the two conditions. This findings suggests that the passage of spermatozoa up to the site of fertilization is under local control and is synchronized with ovulation. The pattern of sperm migration that emerges from these data bears similarities to the pattern in nonprimate species as well as distinctive features. A unique feature in common with the pattern in human is the early establishment of a fairly abundant and persistent sperm population in the ampulla.

Animals

Reversion of insulin resistance in the rat during late pregnancy by 72-h glucose infusion.

To determine whether sustained exaggerated hyperinsulinemia in normoglycemic rats modifies insulin responsiveness during pregnancy, 17-day-pregnant and virgin rats were studied after receiving a continuous intravenous infusion (35 ml/day) of either 50% glucose or bidistilled water (controls) for 72 h. Plasma glucose was unchanged, whereas insulin was highly increased, and the effect was more marked in pregnant than in virgin rats. Insulin responsiveness, estimated under the hyperinsulinemic euglycemic clamp with 0.8 IU insulin.h-1.kg-1, was lower in control pregnant than in virgin rats but higher in pregnant than in virgin rats in those that had received the glucose infusion. The tissue glucose utilization metabolic index (GUI) was estimated with 2-deoxy-D-[1-3H]glucose in the clamped rats. The GUI was lower in heart, white- and red-fiber skeletal muscle, and adipose tissue in control pregnant rats than in control virgin rats, and, although the glucose infusion decreased that index in both red-fiber muscle and adipose tissue in virgin rats, glucose increased the index in red-fiber muscle in pregnant rats to the level found in virgin controls. Results therefore show that, when unaccompanied by hypoglycemia, sustained exaggerated hyperinsulinemia decreases insulin responsiveness in virgin rats but reverts insulin resistance in late-pregnant rats.

Animals

Effect of starvation on lipoprotein lipase activity in different tissues during gestation in the rat.

This study was addressed to determine whether the tissue-specific LPL activity response to fasting differs between nonpregnant and pregnant rats over the course of pregnancy. Fed and 24-h fasted rats were studied at days 12, 15 or 20 of gestation and were compared to virgin controls. In fed rats at days 15 and 20 of gestation LPL activity decreased in lumbar adipose tissue and the heart and liver, and increased in mammary gland tissue. Fasting decreased LPL activity in lumbar adipose tissue in 12 day pregnant and virgin rats and in mammary gland tissue in pregnant rats at 15 and 20 days of gestation and in virgin rats, whereas it increased LPL activity in heart tissue in rats at day 15 and 20 and in liver at day 20 of gestation. Plasma triacylglycerols were higher in 20 day pregnant rats than in the other groups when fed and this difference was even more noticeable in the fasting condition where the plasma beta-hydroxybutyrate level also reached the highest value in the 20 day pregnant rats. Since tissue LPL activity controls the hydrolysis and uptake of circulating triacylgylcerols, the present results indicate that in fed rats after the 15th day of gestation circulating triacylglycerols are preferentially taken up by the mammary gland instead of being taken up by adipose tissue and heart. However, after fasting, circulating triacylglycerols are driven to the heart and liver in the late pregnant rat, and become a major source for fatty acid oxidation, an effect that seems to be specially evident in the liver of the 20 day pregnant rat where there is an intense increase in LPL activity and the triacylglycerols become preferential substrates for ketone body production.

3-Hydroxybutyric Acid

[Changes in the lipid profile in chronic hepatopathies].

BACKGROUND: The pattern of lipoproteins and apolipoproteins has been studied in a group of patients with chronic liver disease. The differences in this pattern were analysed in relation with the stage of liver disease and the presence of cholestasis. METHODS: Twenty one patients with hepatic cirrhosis and 12 with primary biliary cirrhosis were studied. Two subgroups were established according to the disease severity and to the Scheuer classification, respectively. Plasma lipoproteins were separated by ultracentrifugation, and the lipid and apolipoprotein composition were determined. Lipoprotein X was identified by means of agarose gel electrophoresis. RESULTS: In the subgroups with less severe liver disease, only minimal changes were found, such as the decreases in esterified cholesterol and Apo E contents in VLDL in the cirrhotic patients, and the increase of HDL-cholesterol in the patients with primary biliary cirrhosis in the first stages. In patients with severe hepatic cirrhosis, total esterified cholesterol, triglycerides, VLDL and HDL were diminished. Apo E in VLDL was undetectable whereas the different Apo C isoforms were in the normal proportion. Patients with severe biliary cirrhosis showed high levels of total cholesterol and triglycerides, elevated LDL-cholesterol, and decreased HDL-cholesterol and total esterified cholesterol. Apo C-IIO in VLDL was proportionally increased as related to both Apo E and Apo C-III. Lipoprotein X was detected in all these patients and in half of the patients with severe hepatic cirrhosis. CONCLUSIONS: Severe chronic liver disease is associated with a decrease of the concentration of hepatic lipoproteins and the absence of Apo E in VLDL, probably as a result of a defect in their synthesis. The lipid profile found in patients with biliary cirrhosis delineates the pattern of chronic cholestasis, which is characterized by the presence of lipoprotein X, a significant increase of free-cholesterol and a decrease of HDL-cholesterol; VLDL, which are increased, are rich in Apo C-II. Data show the distinct apolipoprotein composition of VLDL in the different hepatic diseases.

Adult

Changes in cholesteryl ester transfer protein activity during normal gestation and postpartum.

Cholesteryl ester transfer protein (CETP) activity was measured in a d > 1.21 kg/L plasma fraction collected from healthy women at different times during gestation, postpartum, and in control women. CETP activity was highest in the second trimester of gestation, declined at the third trimester, and was lowest at postpartum. Only the value at the second trimester was significantly different from that of control women. This trend differed from that of circulating lipoproteins: very low-density lipoprotein (VLDL)-lipids, including triglycerides and cholesterol, increased progressively from the first to the third trimester, and then declined at postpartum. Low-density lipoprotein (LDL)-cholesterol levels, like VLDL levels, rose during gestation but then remained elevated at postpartum. High-density lipoprotein (HDL)-cholesterol as well as HDL-phospholipids and apolipoprotein A-I, peaked in the second trimester, remaining elevated in the third trimester and then fell at postpartum. Finally, HDL-triglyceride increased markedly from the first to the second trimester, rose somewhat higher during the third trimester, and declined at postpartum. When all the samples from pregnant women were considered together, CETP activity correlated significantly with HDL-triglyceride levels and the changes in CETP activity during gestation and postpartum paralleled those of the HDL-triglyceride/VLDL-triglyceride ratio. These results suggest that CETP contributes to the exaggerated accumulation of triglycerides in HDL that begins in the second trimester of human gestation.

Adult

Lipoprotein lipase and hormone-sensitive lipase activity and mRNA in rat adipose tissue during pregnancy.

To investigate the factors controlling maternal depot fat accumulation during early pregnancy and net decrease during late pregnancy, the activity and mRNA expression of adipose tissue lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) were related to several other lipid metabolic parameters. Virgin control rats, pregnant rats (at days 12, 15, 19, and 21), and lactating rats (at days 5 and 10 postpartum) were studied. In adipose lumbar tissue of late pregnant rats, LPL activity decreased to about one-third that of the virgin control animals, with < 10% of initial LPL mRNA expressed as determined by Northern blots. HSL activity increased maximally 1.5-fold with a fourfold increase of HSL expression at days 12-15 of pregnancy and decreased to control levels after parturition. The HSL-to-LPL mRNA and activity ratios were enhanced from days 15 and 19 of pregnancy, respectively, and remained so even during lactation, mainly because of the marked lowering of the LPL values. This enhancement coincided with increments in plasma free fatty acids and glycerol levels indicating an increased depot fat breakdown. These results give no indication of an involvement of LPL and HSL gene expression changes in the accumulation of maternal depot during early pregnancy. In contrast, such changes could be responsible for the net breakdown of this fat depot during late gestation. Thus, during this physiological state, long-term (e.g., transcriptional) regulation of LPL and HSL gene expression could be an important mechanism for the control of adipose tissue mass breakdown during late gestation.

Adipose Tissue

Carbohydrate-lipid interactions during gestation and their control by insulin.

1. During the first two thirds of gestation, coinciding with a minimal accretion by the conceptus, the mother is in an anabolic state which is supported by her hyperphagia and the more efficient conservation of exogenous nutrients when she eats. During this phase maternal fat deposits are accumulated thanks to the enhancement in adipose tissue lipogenic and glycerologenic activity. In contrast, in the latter part of gestation, the rapid fetal growth is sustained by the intense transfer of nutrients from maternal circulation. 2. Glucose is quantitatively the most abundant of the several substrates that cross the placenta and despite increased maternal gluconeogenesis this transfer is responsible for the maternal tendency to hypoglycemia. This causes a switch to a net catabolic state which is especially evident in the net breakdown of fat depots. 3. Enhanced release of adipose tissue lipolytic products, free fatty acids (FFA) and glycerol, facilitates the liver synthesis of triglycerides and their later release into circulation associated to very low-density lipoprotein (VLDL). Glycerol is also used as an important gluconeogenic substrate and FFAs are broken down through beta-oxidation for ketone body synthesis. Flow through these pathways becomes increased when food is withheld and this actively contributes to the availability of fuels to the fetus which becomes partially preserved from maternal metabolic insult. Increased liver production of VLDL-triglycerides and decreased extrahepatic lipoprotein lipase contribute to exaggerated maternal hypertriglyceridemia which, besides being a floating metabolic reserve for emergency conditions such as starvation, constitutes an essential substrate for milk synthesis around parturition in preparation for lactation. 4. While the maternal anabolic tendencies found during the first two-thirds of gestation seem to be facilitated by hyperinsulinemia in the presence of a normal responsiveness to the hormone, it is proposed that most of the metabolic changes taking place during the last third of gestation seem to be caused by the insulin-resistant state which is consistently present at this stage, since its reversion caused by sustained exaggerated hyperinsulinemia also reverts several of these metabolic adaptations.

Adipose Tissue

Cutaneous leishmaniasis in subtropical Ecuador: popular perceptions, knowledge, and treatment.

Popular perceptions and knowledge about cutaneous leishmaniasis and its treatment were studied in an endemic area of subtropical Northwest Ecuador. Although most of the adults surveyed were familiar with the disease, the vector, and traditional treatments, many showed a lack of knowledge about transmission of the disease, ulcer healing, and conventional treatment. Gender was found to have a significant impact on disease risk, perceptions, and treatment knowledge. Males experienced a risk of contracting cutaneous leishmaniasis that was almost triple that of women. Men were also more likely to perceive that the disease seriously diminished the victim's capacity to work. Women, on the other hand, were more prone to perceive that cutaneous leishmaniasis was a serious disease that significantly decreased self-esteem. Although 80% of the subjects knew at least one method of treating the disease, women tended to know more methods than men. Most of 150 different therapies reported involved the use of indigenous plants, chemicals, acids, antibiotics, heat treatments, or petroleum by-products. Some of these treatments could have clinical value. However, only 7% of the subjects knew about pentavalent antimonials. Almost 70% of the subjects with a past or present infection history were treated solely by traditional methods; only 12% received a full course of Glucantime, while 7.5% got an incomplete course. The findings indicate that it will be important to consider the identified gaps in knowledge and gender perceptions regarding the disease and its treatment when planning future control programs.

Adolescent

Cholesteryl ester transfer activity in lipoprotein lipase deficiency and other primary hypertriglyceridemias.

Cholesteryl ester transfer protein (CETP) activity was measured in d > 1.21 g/ml plasma from hypertriglyceridemic patients and compared with normolipidemic subjects. The assay consisted in measuring the specific transfer of [3H]cholesteryl oleate from a prelabelled, apo E-poor HDL fraction to VLDL after incubation at 37 degrees C in the presence of the d > 1.21 g/ml plasma sample: the lipoproteins were then separated by precipitation with dextran sulfate/Mg2+ solution. Increasing the volume of d > 1.21 g/ml plasma or purified human CETP in the assay produced linear responses in measured activity, whereas, either during incubation at 4 degrees C or in the presence of rat plasma instead of human plasma, the transfer of [3H]cholesteryl oleate to VLDL was not stimulated. Thus, the assay reflects changes in CETP in the sample and appears to be suitable for measuring CETP activity in d > 1.21 g/ml plasma. CETP activity was very similar in the two groups of normolipidemic subjects considered: adolescents (203 +/- 11 nmol esterified cholesterol transferred per 8 h/ml plasma) and adults (215 +/- 5). Patients were grouped into lipoprotein-lipase (LPL)-deficient and non-LPL-deficient according to their enzyme activity in postheparin plasma. CETP activity was highly increased in LPL-deficient, severe hyperchylomicronemic patients (430 +/- 42) and was directly correlated with VLDL levels in the non-LPL-deficient individuals. Marked differences were observed in the lipid composition of HDL and apolipoprotein A-I levels among patients and controls. In the control group, CETP activity was correlated only with HDL-triglyceride and HDL-triglyceride/apo A-I mass ratio, which is compatible with the physiological role of CETP in transferring triglyceride to HDL from other lipoprotein particles. When all hypertriglyceridemic patients were considered together, CETP activity was inversely correlated with apo A-I and HDL-cholesterol, whereas it was directly correlated with HDL-triglyceride/HDL-cholesterol and HDL-triglyceride/apo A-I mass ratios. The results indicate that the enhanced CETP activity associated with hypertriglyceridemia contributes to the compositional change of HDL, which in turn may be responsible for the reduction of HDL levels in this condition.

Adolescent

Studies with etofibrate in the rat. Part II: A comparison of the effects of prolonged and acute administration on plasma lipids, liver enzymes and adipose tissue lipolysis.

To contribute to the understanding of the hypolipidemic action of etofibrate, which is the 1,2-ethandiol ester of clofibric acid and nicotinic acid, 300 mg of this drug/kg body weight or of the medium were administered daily by a stomach tube to normolipidemic rats. Some animals were decapitated at the 10th day of daily treatment (prolonged treatment), whereas others were studied at different times after one single administration (acute treatment). In animals on prolonged treatment etofibrate decreased plasma levels of cholesterol, triacylglycerols, free fatty acids (FFA) and glycerol, as well as the total and unesterified cholesterol concentrations, in liver microsomes. In these rats, etofibrate increased the activity of liver cytosolic glycerol-3-P dehydrogenase, whereas it decreased the activity of both microsomal HMG-CoA reductase and cholesterol 7 alpha-hydroxylase and did not affect acyl-CoA: cholesterol acyltransferase (ACAT). At 3, 5 and 7 h after acute treatment, etofibrate decreased plasma levels of triacylglycerols, glycerol and FFA, and this effect disappeared at 24 h, whereas plasma cholesterol did not change 3 h after etofibrate but decreased at 5 and 7 h and remained low after 24 h, and a similar change was found in the liver microsomes free cholesterol concentration. However, with the exception of a significant reduction in cytosolic glycerol-3-P dehydrogenase at 7 h and in ACAT at 5 h, acute etofibrate treatment did not affect the activity of the liver enzymes studied. At low concentrations (10(-5) M) in the incubation medium, etofibrate decreased the release of both FFA and glycerol by epididymal fat pad pieces incubated in vitro. These findings together with those previously reported by us in rats using a similar etofibrate treatment protocol [6] indicate that etofibrate decreases the availability of lipolytic products in the liver by acting on their release from adipose tissue and on their intrinsic hepatic metabolism. Consequently, this drug would decrease liver VLDL triacylglycerol synthesis and secretion, which together with facilitating the clearance of circulating triacylglycerols causes its hypotriglyceridemic effect. The hypocholesterolemic effect of etofibrate after acute treatment may be a secondary consequence of the reduced liver VLDL production caused by decreased adipose tissue lipolysis, but after prolonged treatment, this effect also seems to be influenced by the inhibition of HMG-CoA reductase activity which would reduce cholesterol synthesis.

Adipose Tissue

Interindividual variation in the partition of lipoprotein(a) into lipoprotein subfractions.

In order to evaluate cardiovascular risk, we analyzed the lipid composition of HDL and the presence of lipoprotein(a) [Lp(a)] by both agarose gel electrophoresis and enzyme-linked immunoassay (ELISA). In 681 plasmas we found a close correspondence between the existence of a visible sinking pre-beta lipoprotein band and a concentration of Lp(a) higher than 300 mg/L. In the sinking pre-beta(+) samples, the HDL-cholesterol level obtained by differential ultracentrifugation was significantly higher than that obtained by precipitation with the MgCl2-phosphotungstic acid reagent; and the difference between these HDL-cholesterol values was linearly correlated with plasma Lp(a) concentration. Moreover, the other HDL lipid components and the lipid mass ratios of HDL isolated by ultracentrifugation were significantly different from those of HDL isolated by precipitation, and these changes were also correlated with plasma Lp(a). These differences are attributed to Lp(a) because it was detected in the 1.063-1.21 kg/L plasma fractions, whereas it was absent in the plasma supernates after precipitation with MgCl2-phosphotungstic acid. Although to a lesser extent, Lp(a) was also present in the LDL and VLDL density ranges and it directly depended on both the Lp(a) and the triglyceride plasma concentrations. The proportion of Lp(a) in HDL as related to that in LDL density fractions decreased as Lp(a) plasma levels increased, reflecting an interindividual variation of Lp(a) density species. Since 90% of our study population had detectable Lp(a) in plasma, the results reinforce the concept that the ultracentrifugation method is not equivalent to precipitation in most samples, and the contaminant effect of Lp(a) cannot be predicted because of Lp(a) partition into the different lipoprotein fractions.

Cholesterol, HDL

[Serum lipoprotein (a) levels during treatment with LDL apheresis for homozygous familial hypercholesterolemia].

BACKGROUND: Due to the double atherogenic and antifibrinolytic action of lipoprotein (a) (Lp [a]) and its predictive value of cardiovascular disease in hypercholesterolemic patients, we document in the present work the changes in Lp (a) levels of a patient with homozygous familial hypercholesterolemia after one year of LDL-apheresis treatment. METHODS: A child with LDL-receptor deficiency under weekly LDL-apheresis treatment with dextran-sulfate columns. Serum samples were taken in basal conditions (pre-apheresis) and post-apheresis, as well as from the perfusion system to evaluate the lipoprotein retention capacity of the columns. Samples were processed for Lp (a) determination by ELISA with polyclonal antibodies. RESULTS: When the treatment was initiated, the patient's Lp (a) serum levels were very high (997 mg/l), and they reduced progressively with the apheresis sessions. After one year of treatment, maximum Lp (a) concentration is only slightly higher than 400 mg/l, whereas minimum Lp (a) concentration is lower than 50 mg/l. Dextran-sulfate columns in the apheresis system retain every lipoprotein containing apo B, including LDL and Lp (a), with high affinity and high capacity in such a way that the treatment of three-fold the plasma volume of the patient results in an 85% decrease of Lp (a) levels. After each LDL-apheresis treatment, there is a progressive increase in Lp (a) concentration. The analysis of these data allowed the estimation of the fractional catabolic rate of Lp (a) in the patient, which was 0.08 pools/day. Simultaneous treatment with lovastatin (20 mg/day) did not alter this parameter or Lp (a) serum concentration. CONCLUSIONS: After one year of weekly LDL-apheresis treatment, the patient's average Lp (a) serum concentration is lower than 300 mg/l, which is below the risk threshold level. Therefore, apheresis with dextran-sulfate columns is a very effective treatment for the reduction of both LDL and Lp (a) serum concentrations in homozygous familial hypercholesterolemia.

Blood Component Removal

Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women.

Plasma lipoproteins were studied longitudinally at the 1st, 2nd, and 3rd trimester of gestation and at postpartum and postlactation in 12 age-matched PGDM women, 9 GDM women, and 12 healthy control subjects. FPG and HbA1c were higher in every case in PGDM women than in control subjects, whereas in GDM patients, glucose was augmented only after parturition. FFA and beta-hydroxybutyrate levels were higher in both PGDM and GDM patients than in control subjects during gestation but not after parturition. Total TGs and VLDL, LDL, and HDL TGs increased with gestational time in the three groups and declined at postpartum, and although total cholesterol and VLDL, LDL, and HDL cholesterol followed a similar trend, their rise was less pronounced, and the decline after parturition was slower than that of the TGs in the three groups, with no difference among them. The VLDL TG/cholesterol ratio declined in the three groups at the 3rd gestational trimester, whereas in both LDL and HDL, the TG/cholesterol ratio, but not the cholesterol/phospholipid ratio, increased during gestation in the three groups, indicating a specific enrichment of TGs in these particles. The increase in apoA-I and apoB with gestation was parallel to the respective changes in HDL and LDL cholesterol and, again, no difference was observed between the three groups. Plasma levels of beta-estradiol, progesterone, and prolactin increased sharply with gestation and declined at postpartum in the three groups, but absolute values of beta-estradiol and prolactin, at the three trimesters of gestation, were lower in PGDM patients, but progesterone levels were lower than controls in GDM women only at the 3rd trimester. (ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid