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Biomedical subjects

J Villar

Publications and source records attributed to J Villar.

At least 109 records · Page 6Linked to original sources
PubMed1996

The rate of transbilayer movement of erythrocyte membrane cholesterol is correlated with sodium-lithium countertransport.

Hypertension is associated with some abnormalities in cell membrane structure, including an impaired distribution of cholesterol into the monolayers of erythrocyte membrane. Transbilayer movement of membrane cholesterol modulates the formation of these structural cholesterol domains. We tested whether the rate of cholesterol movement may influence on the erythrocyte Na(+)-Li+ countertransport, that is a marker of human essential hypertension. In single regression analysis, the half-time for the decrease in specific radioactivity of cholestenone (inverse of membrane cholesterol transbilayer movement) was negatively related to the erythrocyte cation flux mediated by Na(+)-Li+ countertransport (r = -0.8983, P < 0.0001 for control subjects; r = -0.8191, P < 0.005 for normocholesterolaemic hypertensive patients; r = -0.7664, P < 0.005 for hypercholesterolaemic hypertensive patients). These data suggest that changes in the transbilayer movement of membrane cholesterol interfere with the main cation transport system which is implicated in the pathophysiology of essential hypertension. This also provides a new link between kinetic cholesterol pools and cell membrane functions.

Antiporters↗
PubMed1996

Plasma lipids, erythrocyte membrane lipids and blood pressure of hypertensive women after ingestion of dietary oleic acid from two different sources.

OBJECTIVE: To study the effect of a diet rich in mono-unsaturated fatty acids (MUFA), from high-oleic sunflower oil (HOSO) and olive oil, on plasma lipids, erythrocyte membrane lipids (including fatty acid composition) and blood pressure of hypertensive (normocholesterolaemic or hypercholesterolaemic) women. METHODS: There were 16 participants who were hypertensive women aged 56.2 +/- 5.4 years. The participants ate a diet enriched with HOSO or olive oil for two 4-week periods with a 4-week washout period before starting the second type of MUFA diet. At entry and during study of each diet, plasma lipids and apolipoproteins were measured by conventional enzymatic methods. Erythrocyte membrane lipid and fatty acid compositions were analysed by means of the latroscan thin-layer chromatography/flame ionization detection technique and by gas chromatography, respectively. Blood pressure was also measured. The statistical analysis was conducted by using Student's two-tailed paired t-test. RESULTS: In both groups of hypertensive patients, there was a significant increase in plasma high-density lipoprotein (HDL) cholesterol concentration after the HOSO or olive oil diets, with regard to baseline. Additionally, a significant decrease in plasma HDL2 cholesterol concentration and an increase in plasma HDL3 cholesterol concentration were evident. The membrane free-cholesterol concentration increased significantly and the phospholipid concentration decreased significantly in erythrocytes after the olive oil diet, though both MUFA diets produced a significant decrease in the concentration of membrane esterified cholesterol. Therefore, the molar ratio of cholesterol to phospholipids was raised significantly in the erythrocyte membrane of hypertensive women after the dietary olive oil, but not after the HOSO diet. In the hypertensive and normo-cholesterolaemic group the HOSO diet significantly increased the content in the erythrocyte membrane of oleic, eicosenoic, arachidonic and docosapentaenoic acids, whereas the olive oil diet increased the content of palmitoleic acid and long-chain polyunsaturated fatty acids of the n-3 family besides, compared with baseline. A significant decrease in linoleic acid was also evident. In the hypertensive and hypercholesterolaemic group, the HOSO diet resulted in significant increases in palmitoleic, oleic, eicosenoic and behenic acids, whereas the olive oil diet enhanced the content of arachidonic, docosapentaenoic and docosahexaenoic acids besides, with respect to baseline. In addition, there was a significant decrease in stearic acid, but only after dietary olive oil was there a decrease in linoleic acid. The most important differences between the two MUFA diets were the increase in n-3 fatty acids and the decrease in the n-6; n-3 fatty acids ratio after dietary olive oil in the erythrocyte membranes of hypertensive patients. Interestingly, a significant reduction in systolic and diastolic blood pressures was only evident after the ingestion of olive oil. CONCLUSION: These data suggest that the beneficial effects of dietary olive oil on the plasma lipids and lipoprotein profile, lipid and fatty acid composition of erythrocyte membrane, and blood pressure in women with untreated essential hypertension are not found equally for the HOSO-rich diet, despite both vegetable oils providing a similar concentration of MUFA.

Aged↗
PubMed1996

Effects of the stress response in septic rats and LPS-stimulated alveolar macrophages: evidence for TNF-alpha posttranslational regulation.

We have previously demonstrated that induction of the stress response, by heat stress or sodium arsenite, administered 18 h before initiation of sepsis in rats, significantly decreased mortality and lung injury. As a possible mechanism underlying this effect, we hypothesized that the induction of the stress response, prior to bacterial endotoxin (lipopolysaccharide, LPS) stimulation, would cause a decrease in synthesis and/or release of tumor necrosis factor-alpha (TNF-alpha), making the animals more resistant to sepsis. Rats exposed to Salmonella typhosa LPS demonstrated a rise in plasma TNF-alpha. In contrast, rats exposed to heat stress or to sodium arsenite 18 h prior to LPS had significantly lower levels of plasma TNF-alpha. To examine the mechanisms by which the stress response mediates this decrease, we studied cultured alveolar macrophages. Similar to in vivo studies, TNF released into supernatants of alveolar macrophages treated with LPS was significantly higher than from cells exposed to the stress response prior to LPS. The decrease in TNF-alpha protein release was not accompanied by a similar decrease in TNF-alpha mRNA levels or by a decrease in cell-associated TNF-alpha, suggesting possible posttranslational regulation of TNF-alpha. To determine whether the decrease in TNF-alpha release was due to binding and sequestration by heat shock proteins (HSP), TNF-alpha was purified by immunoprecipitation. Under these conditions, TNF-alpha and HSP72kDa coprecipitated from cells that had received stress treatment prior to LPS. These data implicate HSP in posttranslational control of TNF-alpha release in LPS-stimulated alveolar macrophages exposed to the stress response.

Animals↗
PubMed1996

Fatty acid composition of lipoprotein lipids in hepatobiliary diseases.

Liver damage and alterations in the exocrine function of the gland lead to a profound alteration of the plasma lipoprotein profile. To determine whether hepatic disease results in changes in the lipoprotein fatty acid composition, i.e. to determine whether liver function influences the homeostasis of complex lipids in plasma, we studied the fatty acid profile of lipids from VLDL, LDL and HDL, as well as from total plasma, in thirty-one patients of both sexes with hepatobiliary pathology (compensated liver cirrhosis, uncompensated liver cirrhosis, primary biliary cirrhosis, other intrahepatic cholestasis, and acute viral hepatitis). We also studied a group of healthy adults as controls. We present the lipoprotein profile and the fatty acid composition (myristic C14, palmitic C16, palmitoleic C16: 1, stearic C18, oleic C18: 1, linoleic C18: 2, eicosatrienoic C20: 3 omega 6 and arachidonic C20: 4) of lipoprotein and total plasma triacylglycerols, cholesteryl esters and phospholipids. The main observation of this study is that, despite the profound changes in the lipoprotein profile and the lower abundance of polyunsaturated fatty acids in complex lipids, the composition of all triacylglycerols, cholesteryl esters and phospholipids is very similar for the corresponding lipoproteins of patients with hepatobiliary disease and of control subjects. This indicates that in the controls as in the studied patients, the exchange of lipids between plasmatic lipoproteins is very rapid and demonstrates the possible importance of the extrahepatic synthesis of cholesteryl ester transfer protein.

Adult↗
PubMed1996

Intrauterine growth retardation at term: association between anthropometric and endocrine parameters.

OBJECTIVE: To investigate the endocrine profile of the intrauterine growth retardation newborns and its association with anthropometric parameters at birth. STUDY DESIGN: This is a case-control study of 76 full term gestations, of which 31 were diagnosed as intrauterine growth retardation (IUGR) confirmed at birth, and 45 as normal births. Insulin, insulin-like growth factor I (IGF-I), growth hormone (GH), thyroid stimulating hormone (TSH), hydrocortisone, prolactin and 15 metabolic parameters were measured in maternal blood antepartum, amniotic fluid and umbilical cord blood at birth. RESULTS: Blood taken from the umbilical cord in the IUGR group had statistically significant lower levels of IGF-I, insulin and TSH, but higher levels of GH. In amniotic fluid and maternal blood, IUGR babies had lower levels of cortisol. The changes in GH and glucose levels in cord blood of IUGR babies were independently associated to birth weight variability (Adjusted regression coefficient-squared=0.09 and 0.17 respectively). Ponderal index (weight/length3) among IUGR babies was independently associated with metabolic changes in amniotic fluid (Adjusted regression coefficient-squared=0.35). CONCLUSIONS: The endocrine profile of IUGR fetus would be: hypoinsulinemic, hypothyrotropinemic, hypoglycemic, hypoalbuminemic, hypocholesterolemic and hypermagnesemic with lower IGF-I levels, yet higher than normal group GH levels at birth. Triglycerides in amniotic fluid; GH, Glucose and Mg changes in cord blood of IUGR babies were independently associated with birth weight variability.

Adult↗
PubMed1996

Modifications induced by -10 degrees Trendelenburg's posture in sodium tubular handling in patients with essential hypertension.

In essential hypertensive patients "exaggerated natriuresis" is a response to acute volume expansion. However, the underlying mechanisms for this remain to be determined. We studied 19 patients with essential hypertension (HP) and 9 normotensive subjects (NS). In all examined subjects the response to acute central volume expansion, without the plasma compositional change that Trendelenburg's position involves, was evaluated during 90 min (period T) after a similar period of deambulation (period D). Mean blood pressure (MBP), tubular sodium handling by the lithium clearance technique, plasma renin activity (PRA), plasma aldosterone (PA), plasma catecholamines and urine prostaglandine E2 and kallikrein were assessed after D and T. MBP was significantly higher in HP than in NS (p = 0.00001). HP showed "exaggerated natriuresis" after T (fractional excretion of sodium increased from 0.55 +/- 0.1% after D to 1.20 +/- 0.2% after T, p < 0.01). This was because of a decrease in their proximal fractional reabsorption of sodium (from 74.96 +/- 1.8% after D to 62.50 +/- 2.8% after T, p < 0.01). Plasma epinephrine and plasma dopamine after T were significantly lower than in standing position in HP (p < 0.01) but no in NS. The decrease in plasma renin activity after T in HP was 53%, and 32% in NS. There were not any significant differences between groups in the other neurohormonal systems studied. We conclude that the major determinant of "exaggerated natriuresis" in hypertensive patients is a higher stimulation of the cardiopulmonary receptors following Trendelenburg's position and consequently stronger reflex inhibition of sympathetic system activity and renin-angiotensin II activity. The "exaggerated natriuresis" after Trendelenburg's position in HP was an expression of abnormal pressure natriuresis.

Adult↗
PubMed1996

Erythrocyte membrane cholesterol distribution in patients with untreated essential hypertension: correlation with sodium-lithium countertransport.

OBJECTIVE: To determine whether the membrane cholesterol distribution is associated with the increased activity of sodium-lithium countertransport in the erythrocytes of normocholesterolaemic and hypercholesterolaemic patients with untreated essential hypertension. METHODS: Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive (normocholesterolaemic and hypercholesterolaemic) patients. The membrane cholesterol distribution between the inner and outer monolayers was measured by means of cholesterol oxidation to cholestenone after continuous cholesterol oxidase treatment. The sodiumlithium countertransport activity was determined by measurements of external sodium (150 mmol/l)-stimulated lithium efflux. The statistical analysis was conducted by analysis of variance with Tukey's correction and correlations were performed by linear regression analysis using Pearson's correlation coefficient. RESULTS: The half-times for cholesterol oxidation were significantly higher in patients with untreated essential hypertension, either with (25.4 +/- 5.6 min) or without (21.7 +/- 2.9 min) concomitant hypercholesterolaemia, than in the controls (15.3 +/- 2.8 min). Sodium-lithium counter-transport activities were also higher in the hypertensive patients (0.410 +/- 0.094 and 0.304 +/- 0.037 mmol/h per litre cell for the hypercholesterolaemic and normocholesterolaemic groups, respectively) than in the controls (0.262 +/- 0.081 mmol/h per litre cell). In single-regression analysis, the half-time for membrane cholesterol oxidation was positively correlated to the erythrocyte cation flux mediated by the sodium-lithium countertransport. CONCLUSION: It is hypothesized that the sodium-lithium countertransport activity might be influenced by membrane structural cholesterol domains.

Antiporters↗
PubMed1996

Erythrocyte Na(+)-Li+ countertransport in essential hypertension: correlation with membrane lipids levels.

OBJECTIVE: To examine whether Na(+)-Li+ countertransport (SLC) activity is linked to erythrocyte membrane lipid content. DESIGN: An observational case-control study. The maximal efflux rate of SLC, plasma cholesterol, triglycerides, phospholipids, low- and high-density lipoprotein cholesterol levels and the erythrocyte membrane cholesterol, phospholipids and fatty acids contents were determined both in fasting normolipaemic normotensive subjects and in hypertensive patients. METHODS: The Li(+)-stimulated Na+ efflux was measured in Li(+)-preloaded erythrocytes. Membrane cholesterol and phospholipids levels were determined by the latroscan technique. Membrane fatty acids were identificated by gas chromatography. Several derived indices were also obtained. RESULTS: Erythrocyte membranes of hypertensive patients showed an increase in cholesterol: phospholipid ratio and a decrease in the total amount of polyunsaturated fatty acids, mainly at the expense of arachidonic acid and docosatetraenoic acid. SLC activity was higher in hypertensive patients and correlated positively with the plasma triglycerides level and negatively with the ratio of C20:4 to C20:3. CONCLUSION: Our data from untreated normolipaemic hypertensive patients show that a higher SLC activity was accompanied by parameters that indicate a lower membrane fluidity.

Adult↗
PubMed1995

Predictive ability of meta-analyses of randomised controlled trials.

Although meta-analysis of randomised clinical trials is increasingly used, the evaluation of its ability to predict the results of large trials is not available. We have calculated the relative risks (and 95% confidence intervals) for thirty meta-analyses of different interventions in perinatal medicine, covering 185 randomised controlled trials, but with the largest trial removed. We then compared those results with the result of the largest trial (total sample size more than 1000) done on that intervention and outcome. Twenty-four meta-analyses correctly predicted the direction of the treatment effect, but only eighteen of the thirty were the same both in direction of treatment effect and in statistical significance as the largest trial. There was moderate agreement, beyond chance, between meta-analysis and largest trial results (kappa statistic 0.46-0.53). A meta-analysis demonstrating a protective effect from an intervention of more than 40% had a 60% probability of correctly predicting results of the same magnitude of the largest trial. Researchers and funding agencies may use meta-analysis before recommending a clinical practice or to summarise results of three controlled trials before deciding on additional studies of promising interventions. However, further evaluation of the meta-analytical method is needed if the qualitative and quantitative results it yields are to be better understood.

Confidence Intervals↗
PubMed1995

Description of a new quotient that may differentiate blood pressure profiles in essential versus Cushing's syndrome-related hypertension.

Since the presence or absence of a nocturnal decrease in blood pressure values (BP) may suggest an increased risk of visceral complications or the existence of secondary hypertension, several methods have been described for evaluating the BP profile. Nevertheless, a universally accepted system to evaluate this item has not yet been established. Our aim in this study was to test different dispersion quotients (DQ) which estimate the differences between the mean of each hour, and the mean of all the readings in the 24 h period. These quotients may be employed regarding systolic (SBP) or diastolic (DBP) blood pressure, and may be referred to the whole period of 24 h, or to the subperiods morning (m), afternoon (a) or night (n). We have studied two non selected groups of essential (n = 20) or secondary (Cushing's syndrome, n = 17) hypertensives. We observed a marked decrease in these quotients, particularly DQ-SBP and nDQ-SBP, in secondary hypertensives (respectively 10.2 +/- 2.9 vs 15.6 +/- 4.2 and 11.8 +/- 5.0 vs 20.5 +/- 6.3, p < 0.0001), thus indicating, a blunted nocturnal fall of BP in these patients. Also the DQ and particularly DQ-SBP, nDQ-SBP and nDQ-DBP, showed a high positive and negative predictive value, sensitivity and specificity for pertaining to the Cushing's syndrome group (respectively: 0.75, 0.88, 0.88, 0.75; 0.86, 0.82, 0.77 0.90; and 0.78, 0.84, 0.82, 0.80).

Adolescent↗
PubMed1995

Impact of health education during pregnancy on behavior and utilization of health resources. Latin American Network for Perinatal and Reproductive Research.

OBJECTIVE: Our purpose was to assess whether an intervention in the education of the mother and the support person involves a change in health-related behavior and use of health facilities. STUDY DESIGN: A randomized, controlled trial was conducted in four cities of Latin America on pregnant women at risk. Half of them (n = 1115) received a home intervention of four to six visits dealing with psychosocial support and education about health-related habits, alarm signs, hospital facilities, antismoking and antialcohol programs, and a reinforcement of adequate health services utilization for the pregnant woman and a support person. The control group (n = 1120) received routine prenatal care. RESULTS: The distribution of risk factors and demographic, obstetric, and psychologic characteristics at baseline was similar in both groups. Women in the intervention group showed a statistically significant better knowledge of seven of the nine alarm signs considered and of two of the three labor-onset signs required. No differences between groups were observed in improvement on diet, cigarette and alcohol consumption, maternal physical strain, lactation at 40 days postpartum, and utilization of health facilities. CONCLUSIONS: An intervention of psychosocial support and health education during pregnancy failed to show any benefit on perinatal outcome, health-related behavior, or utilization of health facilities.

Alcohol Drinking↗
PubMed1995

Transbilayer movement of erythrocyte membrane cholesterol in human essential hypertension.

OBJECTIVE: To study whether the rate of transbilayer movement of membrane cholesterol is impaired in erythrocyte membrane of normo- and hypercholesterolaemic patients with untreated essential hypertension. DESIGN: An observational case-control study. METHODS: Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive patients. The rate of transbilayer movement of membrane cholesterol was monitored in intact erythrocytes, using a radiolabelled cholesterol tracer. Erythrocytes were treated briefly or continuously with cholesterol oxidase to convert a portion of the outer leaflet cholesterol to cholestenone, and the specific radioactivity of cholestenone was determined over the period of tracer equilibration. The decrease in specific radioactivity of cholestenone reflected the transbilayer movement of radiolabelled cholesterol. RESULTS: There were no significant differences between the diffusion of cholesterol across the erythrocyte membrane of normo- and hypercholesterolaemic hypertensive patients, but the rates were significantly lower than that estimated in control subjects. The mean +/- SD half-times for the process were 55.1 +/- 8.8 and 11.3 +/- 2.1 min in controls, 63.1 +/- 9.2 and 15.8 +/- 2.3 min in normocholesterolaemic hypertensive patients, and 66.2 +/- 9.4 and 16.2 +/- 1.7 min in hypercholesterolaemic hypertensive patients, after a brief and after a continuous cholesterol oxidase treatment, respectively. CONCLUSION: There is a reduction in the transbilayer movement of membrane cholesterol in erythrocytes of patients with untreated essential hypertension.

Adult↗
PubMed1995

Ultrastructural study of the early development of the sheep embryo.

An ultrastructural study of the different stages of pre-implantation in sheep was carried out, analysing the changes brought about mainly in the morula and blastocyst stages. The analysis of the embryos obtained showed a series of common characteristics in all stages, most noticeable being the presence of a high number of vesicles distributed in a uniform way in the cytoplasm, and also the presence of numerous electron-dense mitochondria in many varied forms. The most important ultrastructural modifications took place at the 16-cell stage and affected, principally, the nucleus, which presented numerous condensations of chromatin distributed along the nucleoplasm. The nucleoli adopted a reticular morphology, abandoning the compact aspects presented in the previous stage. These changes might be involved in the synthesis of embryonic RNA, and, accordingly, in the activation of the genome of this species. These data indicate that this stage is critical to the embryonic development and might be related to the blockage produced in the development of cultivated sheep embryos at the point of transition from 8 to 16 cells. Nevertheless, it should be pointed out that the first signs of modifications in the aspect of the nucleus are observed at the four-cell stage, being characterized by the appearance of vacuolated areas in the nucleolus, indicating the first signs of embryonic nucleic activity, which would anticipate the main change in the control of the protein synthesis.

Animals↗
PubMed1995

Induction of the stress response to prevent organ injury.

Septic shock, multiorgan dysfunction, and the acute respiratory distress syndrome are major contributors to morbidity and mortality in the ICU setting. Animal studies have shown that these forms of injury can be attenuated or prevented if a phenomenon, called the stress response, is activated. The stress response, characterized by a transient downregulation of most cellular products and by the upregulation of the heat-shock proteins (HSPs), has been shown to provide protection to cells and experimental animals if triggered prior to an otherwise lethal injury. The mechanisms by which the stress response is protective are not known with certainty, but HSPs appear to play an important role. HSPs are constitutively present in all cells studied to date and can also be induced by artificial fever and by nonthermal means. They act as molecular chaperones, interacting transiently with newly synthesized proteins and proteins experiencing difficulty in proper folding. HSPs also escort and help proteins to cross membranes. This chaperone function is essential for cellular protection since it provides a mechanism by which defective polypeptides may be directed to lisosomes for degradation. This article summarizes the current literature on the effects of the stress response in protecting cells and animals from lethal forms of systemic and organ damage.

Animals↗
PubMed1995

A rapid community based health evaluation of pregnant women in low socioeconomic settlements of Karachi.

A rapid nutritional and health evaluation of a random sample of 163 pregnant women was conducted in low socioeconomic settlements of Karachi, with the objective of determining the morbidity and nutritional status of pregnant women. These data are expected to be used in an ongoing community-based antenatal care programme. Twenty-nine percent of women reported fever, 14 percent diarrhoea and 33 percent respiratory infections in the previous week. Mean weight was 54.8 (+/- 10.6) kg, mean height was 151.6 (+/- 6.0) cm and mean midarm circumference was 25.6 (+/- 3.2) cm. The mean uterine height at gestational ages 8 months and over was 32.1 (+/- 10.2) cm which is below the 10th percentile. These results suggest a chronic, mildly malnourished population with a high rate of infections. Specifically, we suggest that maternal height and uterine height be used to assess women at high risk for low birthweight.

Anthropometry↗