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Biomedical subjects

M Esteve

Publications and source records attributed to M Esteve.

At least 73 records · Page 4Linked to original sources

Lipid synthesis: a thermogenic mechanism in cold-exposed Zucker fa/fa rats.

1. The oxygen consumption and carbon dioxide production of Wistar and Zucker lean (Fa/?) and obese (fa/fa) rats was measured at 4, 10, 20 and 30 degrees C. 2. There was a net synthesis of lipid at the expense of carbohydrate in Wistar rats at 20 degrees C, with active lipid oxidation at 4 degrees C, and increasing heat production at lower temperature. Zucker lean rats also showed this trend. 3. Zucker fa/fa rats synthesized lipid at 4, 10 and 20 degrees C, showing a less marked increase in heat production with lowering temperature. 4. It is postulated that Zucker obese rats synthesize lipids as a way to obtain residual metabolic heat to maintain their body temperature. This is part of a process--fully functional in Wistar and Zucker lean rats, and truncated in Zucker obese rats--in which liver lipogenesis can combine with brown adipose tissue lipolysis to generate enough heat to maintain body functions under a cold environment.

Animals↗

Intestinal and hepatic nitrogen balance in the rat after the administration of an oral protein load.

The fate of a small oral dose of protein given to overnight-starved rats was studied. After 3 h, 62% of the protein amino acids had been absorbed. Most of the absorbed N went into the bloodstream through the portal in the form of amino acids, but urea and ammonia were also present. About one-quarter of all absorbed N was carried as lymph amino acids. The liver was able to take all portal free ammonia and a large proportion of portal amino acids, releasing urea. The hepatic N balance was negative, indicating active proteolysis and net loss of liver protein.

Amino Acids↗

Methodological evaluation of indirect calorimetry data in lean and obese rats.

1. The applicability of current indirect calorimetry formulae to the study of energy and substrate balances on obese rats has been evaluated. The energy consumption of series of 60-day rats of Wistar, lean and obese Zucker stock were studied by means of direct and indirect calorimetry, and by establishing their energy balance through measurement of food intake and retention. Calorimetric studies encompassed a 24 h period, with gas and heat output measurements every 2 or 5 min, respectively, for direct and indirect calorimetry. 2. The analysis of fat composition (diet, whole rat, and synthesized and oxidized fat) showed only small variations that had only a limited effect on the overall energy equation parameters. 3. A gap in the nitrogen balance, which represents a urinary N excretion lower than the actual protein oxidized, resulted in significant deviations in the estimation of carbohydrate and lipid oxidized when using the equations currently available for indirect calorimetry. 4. Analysis of the amino acid composition of diet and rat protein as well as of the portion actually oxidized, and correcting for the nitrogen gap allowed the establishment of a set of equations that gave better coincidence of the calculated data with the measured substrate balance. 5. The measured heat output of all rats was lower than the estimated values calculated by means of either indirect calorimetry of direct energy balance measurement; the difference corresponded to the energy lost in water evaporation, and was in the range of one-fifth of total energy produced in the three rat stocks. 6. Wistar rats showed a biphasic circadian rhythm of substrate utilization, with alternate lipid synthesis/degradation that reversed that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did not show this rhythm; obese rats synthesized large amounts of fat during most of the light period, consuming fat at the end of the dark period, which suggests more diurnal feeding habits. Lean Zucker rats showed a similar, but less marked pattern. 7. The results obtained indicate that lean and obese rats can be studied using the same indirect calorimetry formulae provided that there is an adequate measure of protein oxidation and the composition of diet does not differ.

Amino Acids↗

In vitro and in vivo antibacterial activities of E-4868, a new fluoroquinolone with a 7-azetidin ring substituent.

E-4868, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-(2,4- difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid, is a new fluoroquinolone with an azetidine moiety at the 7 position. The in vitro activity of E-4868 has been compared with those of ciprofloxacin, ofloxacin, and fleroxacin, while the activity of ciprofloxacin was used as reference for in vivo studies. The MICs of E-4868 for 90% of the isolates tested (MIC90s) were 0.06 to 0.5 microgram/ml against gram-positive organisms, including Staphylococcus, Streptococcus, and Enterococcus spp. In general, the in vitro potency of E-4868 against gram-positive bacteria was higher than those of all of the other fluoroquinolones tested. MIC90s against members of the family Enterobacteriaceae between 0.03 and 1 microgram/ml were observed, with the exception of those against Serratia marcescens and Providencia spp., and a MIC90 of 2 micrograms/ml against Pseudomonas aeruginosa was obtained. E-4868 inhibited 90% of the Clostridium spp. and Bacteroides spp. at 2 micrograms/ml and was twofold more active than ciprofloxacin. An increase in the Mg2+ concentration from 1 to 10 mM increased the MIC between two and three times. Human urine caused a significant decrease in activity of E-4868, which was more pronounced at pH 5.5 than at pH 7.2. The presence of serum also decreased the activity of E-4868. Fifty percent effective dose (ED50) values against experimental Escherichia coli HM-42 infections in mice were 3.9 mg/kg of body weight with E-4868 and 3.5 mg/kg of body weight with ciprofloxacin. Corresponding ED50 values against P. aeruginosa HS-116 were 93.2 and 107.8 mg/kg, respectively, and those against Staphylococcus aureus HS-93 were 6.5 and 44.6 mg/kg, respectively. In experimental infections with Streptococcus pneumoniae 84551, the ED50 value of E-4868 was 154.4 mg/kg, while ciprofloxacin proved totally inactive at a dose of 400 mg/kg. When E-4868 was administered orally at a dose of 50 mg/kg in mice, the area under the concentration-time curve (0 to 4 h) value was 28.4 microgram . h/ml, while an area under the concentration-time curve value of 2.3 microgram . h/ml was observed for ciprofloxacin at the same dose. In these studies, levels of the two agents in blood 1 h postadministration were 7.6 and 1.2 microgram/ml, respectively.

Animals↗

Polymeric enteral diets as primary treatment of active Crohn's disease: a prospective steroid controlled trial.

Thirty two patients with active Crohn's disease were included in a controlled randomised trial to determine the efficacy and safety of polymeric enteral nutrition compared with steroids, to achieve and maintain clinical remission. The polymeric diet was administered through a fine bore nasogastric tube by continuous, pump assisted infusion (2800 (SEM 120) kcal/day). The steroid group received 1 mg/kg/day of prednisone. Both treatments were effective in inducing clinical remission: 15 of the 17 patients given steroids and 12 of the 15 patients assigned to the polymeric diet went into clinical remission (defined by a Van Hees index < 120) within four weeks of treatment. The percentage reduction of the Van Hees index was 34.8 (4.9)% for steroids and 32.3 (5)% for enteral nutrition (mean difference 2.5%; 95% CI--11.8% to +16.8%). Mean time elapsed to achieve remission was similar in both groups (2.0 (1) v 2.4 (1.2) weeks). Tolerance of the enteral diet was excellent. Four patients in the steroid group had mild complications attributable to this treatment. Ten patients (66.6%) in the steroid group and five (41.6%) in the enteral nutrition group relapsed within a year of discharge, but no differences were found in the cumulative probability of relapse during the follow up period. These results suggest that polymeric enteral nutrition is as safe and effective as steroids in inducing short term remission in active Crohn's disease.

Acute Disease↗

Clinical and nutritional factors predictive of plasma lipid unsaturation deficiency in advanced liver cirrhosis: a logistic regression analysis.

AIM: To identify those clinical and nutritional factors associated with plasma lipid unsaturation deficiency in cirrhosis. METHODS: Fatty acid profiles of plasma phospholipids (PL) and cholesteryl esters (CE) were measured in 101 inpatients with advanced cirrhosis and in 44 age- and sex-matched healthy controls. Double-bond index (DBI) was calculated for each fraction and binarily categorized in each patient using the 5th percentile of the control group as the cut-off limit. The association of 12 routine clinical, biological, and nutritional variables with derangement of each DBI was multivariately assessed by means of stepwise logistic regression analysis. RESULTS: The DBI of PL and CE were below the 5th percentile of the control group in 60 and 68 of 101 cirrhotic patients, respectively. After multivariate analyses, the variables found to be independent predictors of impaired unsaturation were: 1) The presence of moderate/severe malnutrition (odds ratio: 1.3-8.0 (95% CI); p < 0.05) and serum tau-GT > 1 mukat/L (odds ratio: 0.2-1.0; NS) for plasma PL, and 2) the presence of moderate/severe malnutrition (odds ratio: 1.8-17.4; p < 0.05), serum bilirubin > 50 mumol/L (odds ratio 1.7-14.5; p < 0.05) and serum tau-GT > 1 mukat/L (odds ratio 0.1-1.1; NS) for CE. CONCLUSION: Malnutrition appears to be a major factor for impaired lipid unsaturation in advanced cirrhosis. Thus, the possibility of improving plasma lipid unsaturation in these patients by means of nutritional support should be further investigated.

Adult↗

Dietary amino acid balances in young Wistar rats fed a cafeteria diet.

The amino acid composition of the diet ingested by reference and cafeteria diet-fed rats has been analyzed in Wistar rats from day 30 to 60 after birth. Body protein amino acid composition and the urinary and faecal losses were also measured. Cafeteria diet resulted in a higher proportion of amino acids extracted from the diet, although this diet had a very similar amino acid composition to that of the standard reference diet. The net rates of amino acid accretion into body protein were similar for cafeteria and reference diet-fed rats, resulting in a comparable net overall accumulation of protein. Urinary losses of amino acids were small, but higher for reference diet-fed rats. Cafeteria feeding leads to an essentially equal amino acid intake pattern to that resulting from the reference diet. In addition, cafeteria-feeding resulted in a similar amino acid nitrogen intake and practically equal amino acid availability, which is translated into higher net protein accrual and lower nitrogen losses in cafeteria-fed rats. It is postulated that the lower protein-energy proportion of the cafeteria diet--and not its amount in absolute terms--could trigger a series of amino acid-sparing mechanisms that eventually result in even higher amino acid availability, which leads to increased net protein deposition and a wider nitrogen gap.

Amino Acids↗

Routine tests of renal function, alcoholism, and nutrition improve the prognostic accuracy of Child-Pugh score in nonbleeding advanced cirrhotics.

In an attempt to improve the prognostic capacity of Child-Pugh score in nonbleeding cirrhotics, 110 consecutive in-patients without gastrointestinal hemorrhage at admission were studied and followed up for 24 months or until death. Fifty-five of the 110 patients (50%) died during this period. Mean survival time was 18.8 +/- 1.4 months (mean +/- SEM). In addition to Child-Pugh score, eight variables, including anthropometric nutritional parameters, routine renal function tests, and alcoholism markers, were recorded at admission. The ability of these variables to improve the prognostic capacity of the Child-Pugh score was assessed with the proportional hazard Cox's regression procedure, using a stepwise method for covariate selection, after including the Child-Pugh score at the first step. Thus, in addition to Child-Pugh score (beta = 0.302), three variables were included in the final model: serum urea (beta = 0.113), MCV (beta = 0.027), and mid-arm muscle circumference (beta = -0.025). According to the contribution of each of these factors to the model, a prognostic index was obtained to estimate survival in the individual patient. An assessment of the predictive power of the model was made by means of a split-sample technique. The prognostic index described in this study may contribute to improve the selection of nonbleeding patients with advanced cirrhosis to receive specific therapies such as transplantation. However, its true clinical relevance will be established only by prospectively comparing its prognostic value with that of the Child-Pugh score in a new sample of patients.

Alcohol Drinking↗

Fatty acid utilization by young Wistar rats fed a cafeteria diet.

The content and accretion of fatty acids in 30, 45 and 60-day old Wistar rats fed either reference chow or a cafeteria diet has been studied, together with their actual fatty acid intake during that period. Diet had a small overall effect on the pattern of deposition of fatty acids, but the deposition of fat was much higher in cafeteria rats. The fat-rich cafeteria diet allowed the direct incorporation of most fatty acids into lipid storage, whilst chow-feeding activated lipogenesis and the deposition of a shorter chain and more saturated type of fatty acids. During the second month of the rat's life, the elongation pathway as well as delta 9-desaturase became functional, thus helping to shape the pattern of fatty acids actually accrued. The 60-day rats showed a relative impairment in the operation of delta 5-desaturase, since their lipids had a higher C20:4/C20:3 ratio than those of the diet ingested. Cafeteria-diet feeding minimized this effect since the large supply of dietary polyunsaturated fatty acids made the operation of the elongation-desaturase pathways practically unnecessary.

Aging↗

Factors related to the plasma fatty acid profile in healthy subjects, with special reference to antioxidant micronutrient status: a multivariate analysis.

The plasma lipid fatty acid (FA) profile was measured in 83 healthy subjects (35 men, 48 women; ages 18-82 y). The association of 19 variables (including serum antioxidant micronutrients) with saturated (SFA), monounsaturated (MUFA), essential (EFA), and polyunsaturated fatty acid (PUFA) status was assessed by stepwise multiple-linear regression. Serum selenium was directly associated with percent EFA and n-6 PUFA (r = 0.38, P = 0.0004 for both) and inversely related to percent SFA in phospholipids (r = -0.38, P = 0.0004). Serum selenium was the only predictor of the unsaturation index of this fraction (r = 0.45, P = 0.0000). Although associations of plasma FA pattern with age, serum cholesterol, bilirubin, vitamin E, and zinc were also disclosed, only for selenium did the antioxidant effect seem to explain this relationship. These results suggest that antioxidant micronutrients should be measured when PUFA metabolism is studied. The relationship between plasma FA and antioxidant micronutrients in disease states needs further research.

Adolescent↗

Nitrogen balances of lean and obese Zucker rats subjected to a cafeteria diet.

The effects of a cafeteria diet on nitrogen balance in lean (Fa/?) and obese Zucker rats (fa/fa) was studied for two consecutive 15 day periods after weaning. Obese rats were able to absorb a lower proportion of dietary nitrogen than the lean controls. Cafeteria diet increased the retention of dietary nitrogen, and lowered urinary nitrogen losses in both obese and lean rats. Urea constituted practically the only product of urinary nitrogen excretion in obese rats, whereas it accounted for only about 75% of that eliminated by Fa/? rats. Nitrogen accretion in the body was highest for the younger animals, and again increased with cafeteria feeding. Obese fa/fa rats showed a lower percentage of body nitrogen retention than their lean counterparts; obese rats were able, however, to accumulate large amounts of nitrogen and fat, in part because of their higher intake. A significant part of the absorbed nitrogen was not found in either the body or the urine; the cafeteria diet markedly increased the weight of this fraction of nitrogen unaccounted for. In conclusion, the effects of cafeteria feeding on weight and nitrogen handling were comparable in lean and obese rats, i.e. the effects of genetic and dietary obesity seem to be additive with regard to nitrogen extraction and excretion for Zucker rats.

Absorption↗

Deposition of dietary fatty acids in young Zucker rats fed a cafeteria diet.

The content and accretion of fatty acids in 30, 45 and 60-day-old Zucker lean Fa/? and obese fa/fa rats fed either reference chow or a cafeteria diet has been studied, together with their actual fatty acid intake during each period. Diet had little overall effect on the pattern of deposition of fatty acids, but quantitatively the deposition of fat was much higher in cafeteria-fed rats. The fat-rich cafeteria diet allowed the direct incorporation of most fatty acids into the rat lipids, whilst chow feeding activated lipogenesis and the deposition of a shorter chain and more saturated pattern of fatty acids. Genetic, obesity induced a significant expansion of net lipogenesis when compared with lean controls. Cafeteria-fed obese rats accrued a high proportion of fatty acids, which was close to that ingested, but nevertheless showed a net de novo synthesis of fatty acids. It is postulated that the combined effects of genetic obesity and a fat-rich diet result in high rates of fat accretion with limited net lipogenesis. Lean Zucker rats show a progressive impairment of their delta 5-desaturase system, a situation also observed in obese rats fed a reference diet. In Zucker obese rats, cafeteria feeding resulted in an alteration of the conversion of C18:2 into C20:3. The cafeteria diet fully compensated for these drawbacks by supplying very high amounts of polyunsaturated fatty acids.

Animals↗

Rat intestinal amino acid balances after the administration of an oral protein load.

The intestinal amino acid balances in rats given an oral load of protein were measured three hours after the gavage. During that period, about one half of the nitrogen from the protein given appeared as net balance in the portal blood. The release of amino acids was not a continuous process, since two peaks of maximal intestinal efflux were found at 1 and 2.5 hours after gavage. This pattern followed that of portal blood flow with a 30 minute delay. Under prandial conditions, the intestine showed a net uptake of glutamine, aspartate, serine, threonine, phenylalanine, tyrosine, leucine, isoleucine and valine. It also showed a net production of alanine, glutamate, ornithine skeleton (arginine + citrulline + ornithine) and ammonia. There was also a surge of taurine, attributed to reabsorption of secreted taurine conjugates. There was a net unchanged absorption of glycine, proline, lysine and histidine, with respect to their proportions in the protein administered. The results suggest that the amino acid metabolism in the intestine under prandial conditions is much less passive than is generally assumed. The intestinal action upon the luminal amino acids is not limited to absorption, but is directly implied in their transformation to complement the ensuing homeostatic action of the liver upon them.

Amino Acids↗

Nitrogen balance discrepancy in Wistar rats fed a cafeteria diet.

The nitrogen balance of Wistar rats aged 30-45 and 45-60 days fed either control or cafeteria diet has been determined by measuring the intake fecal and urinary excretion and nitrogen deposition in the body. The efficiency of extraction of dietary nitrogen was higher for cafeteria diet-fed rats, which showed a lower nitrogen excretion and higher body nitrogen accretion than controls. The accurate measurement of nitrogen intake, excretion and deposition showed a consistent proportion of nitrogen unaccounted for (10-26% of net intake) in the studied fractions, which proportion was higher in the youngest cafeteria diet-fed rats.

Animals↗

[The evidence of human immunodeficiency virus infection in the seronegative subjects of high-risk groups].

BACKGROUND: Polymerase chain reaction (PCR) is a new diagnostic procedure which has been used to recognise HIV-infected individuals who remain seronegatives. METHODS: Genomic DNA isolated from the peripheral blood mononuclear cells of 90 high-risk individuals were analyzed by PCR using gag primers SK 38/39. Subjects were classified in four groups: 42 drug abusers, 35 heterosexual partners of HIV-infected individuals, 9 homosexual men, and 4 health care workers accidentally exposed to HIV. Liquid hybridization using radiolabelled probes was done to confirm the results. All samples were also tested for HIV antigen and antibodies (Ab) using EIA and Western blot (WB). RESULTS: Two out of 11 (18%) drug abusers and 5 out of 34 (14%) couples were PCR positive in absence of HIV antibodies. This silent HIV infections were not recognized in homosexuals and health care workers. All 38 seropositive samples were PCR positive. None of the samples PCR+/Ab- was positive for HIV antigenemia or showed indeterminate results in the WB assay. CONCLUSIONS: Silent HIV infections were recognized in drug abusers (18%) and couples of HIV-infected individuals (14%). Mechanisms involved in the production of this "occult" HIV infections are reviewed.

HIV Antibodies↗

Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients.

Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population.

Adult↗

[Prevention by naloxone of adverse effects of epidural morphine analgesia for cancer pain].

Forty cancer patients were randomly assigned to two groups (n = 20). All had incapacitating pain unresponsive to the usual non opioid analgesic drugs. An epidural catheter was set up at the level of the most painful metamere, and made to pass subcutaneously so as to exit either in the supraclacicular fossa, or on the patient's flank. At T0, the patients were given 4 mg morphine hydrochloride diluted in 10 ml normal saline. Thirty min later, patients in the naloxone group (group N) were given a 0.4 mg bolus, followed by a constant rate infusion of 5 micrograms.kg-1.h-1, of naloxone hydrochloride during 18 h. Patients in group P (placebo) were given normal saline instead. The degree of pain was studied with a visual analogue scale and analgesia was assessed by a clinician on a five point scale. These two parameters were obtained half an hour after the injection of morphine and 2, 4, 6 and 24 hours later. At the same time, the patients were questioned about adverse side-effects: nausea, vomiting, pruritus, dysuria, urinary retention. Respiratory depression was assessed clinically and biologically (blood gas measurements at the afore mentioned times). Heart rate, systolic and diastolic blood pressure were also measured. There was no statistically significant difference between the groups in quality and duration of analgesia. Pain reached its lowest level 4 h after the injection of morphine, returning to half its original value at the 24th h. This was also true for the incidence of nausea (11 in group N, 5 in group P), vomiting (3 in both groups), and urinary retention (6 in group P, 5 in group N).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro and in vivo antibacterial activities of E-4497, a new 3-amine-3-methyl-azetidinyl tricyclic fluoroquinolone.

The in vitro and in vivo antibacterial activities of a new tricyclic fluoroquinolone, E-4497 [S(-)-9-fluoro-3-methyl-10-(3-amine-3-methyl-azetidin-1-yl)-7-oxo- 2,3-dihydro- 7H-pyrido-(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid], were evaluated in comparison with those of DR-3355 [S-(-)-ofloxacin], norfloxacin, and ciprofloxacin. E-4497 was more potent than norfloxacin and as potent as or more potent than DR-3355 and ciprofloxacin against Staphylococcus spp., Streptococcus spp., and Enterococcus faecalis. With the exception of Providencia spp., E-4497 inhibited 90% of the Enterobacteriaceae at less than or equal to 0.25 micrograms/ml. Against enteric bacteria, E-4497 was similar in potency to norfloxacin but less potent than DR-3355 and ciprofloxacin. For Pseudomonas aeruginosa, the MICs of E-4497, DR-3355, norfloxacin, and ciprofloxacin for 90% of strains were 2, 2, 4, and 0.5 micrograms/ml, respectively. Against Clostridium perfringens and Bacteroides fragilis, E-4497 (MICs for 90% of strains, 2 and 8 micrograms/ml, respectively) was two- to fourfold more active than norfloxacin and ciprofloxacin. E-4497 activity decreased moderately in the presence of 10 mM Mg2+. Urine at pH 5.5 caused a significant decrease in activity compared with urine at pH 7.2. However, the presence of serum either had no effect or increased the activity of E-4497. In general, E-4497 was bactericidal at the MIC. In systemic infections with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa in mice, the protective effect of E-4497 was generally greater than that of norfloxacin and comparable to those of DR-3355 and ciprofloxacin.

Animals↗