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Biomedical subjects

R Jimenez

Publications and source records attributed to R Jimenez.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effect of the quality of infused energy on substrate utilization in the newborn receiving total parenteral nutrition.

Newborn infants (n = 26), subdivided into three groups in which only the nonprotein energy was manipulated, were studied during continuously administered total parenteral nutrition. Nonprotein energy intake was provided as a glucose/fat mixture, and fat energy represented 18% (group A), 29% (group B), and 40% (group C). Energy expenditure and substrate utilization were measured by indirect calorimetry during a 6-h period. Other analyses included 24-h urinary nitrogen excretion, glycemia, and lipid profile. The results showed that glucose oxidation increased with increasing total glucose intake (p < 0.05). Net fat oxidation was observed in all groups and increased with increasing percentage of energy infused as fat. The maximal oxidative glucose disposal rate observed was in group A (11.2 g/kg/d). Maximal fat oxidation observed was in group C (2 g/kg/d), in which energy delivered by fat represented 40%. This group was more energy efficient than the others. Oxygen consumption was not affected by modification of the source of energy, but carbon dioxide production was higher in group A (p < 0.05), as was the nonprotein respiratory quotient (p < 0.05). Despite differences in carbon dioxide production, arterial capillary PCO2 was not affected and, together with the higher (p < 0.05) minute ventilation, suggests that adequate pulmonary compensation occurred during the low-fat regimen. Arterial capillary PO2 was lower during the high-fat regimen (p < 0.05). Protein oxidation was greater in group A (1.14 +/- 0.32 g/kg/d) than in group B (0.70 +/- 0.21 g/kg/d) or group C (0.78 +/- 0.28 g/kg/d).(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Carbohydrates↗
PubMed1993

Effects of a hypercholesterolaemia-inducing diet on biliary electrolytes and lipid secretion in the rat.

The effects of a high cholesterol/cholate diet on the biliary secretion of bile acids, cholesterol, phospholipid and inorganic electrolytes in the rat were examined. Wistar rats were fed a hypercholesterolaemia-inducing diet (HID) for 20 days prior to the biliary experiments. Rats fed a standard laboratory diet were used as controls. The HID diet increased plasma cholesterol concentrations and the hepatic content of total, free and esterified cholesterol, without changes in ALP*, ALT and AST plasma activities. Bile flow and biliary secretion of bile acids and inorganic electrolytes were markedly increased in the hypercholesterolaemic animals. The stimulated biliary secretion was due to an increase in both the bile acid-dependent and bile acid-independent fractions of bile flow. An increase in the bile acid pool induced by the administration of exogenous cholic acid/cholesterol would account for these changes in bile flow and inorganic electrolyte secretion. Nevertheless, the increase in the bile acid-independent bile flow could be also related, at least to some extent, to a higher efficiency of bicarbonate transport into bile. The HID diet also increased both cholesterol and phospholipid biliary outputs, whereas it did not modify the relationship between lipid and bile acid secretion. The lithogenic index of bile was reduced in the rats after the HID regimen due to a relatively higher increase in the biliary outputs of phospholipids and bile acids than of cholesterol.

Animals↗
PubMed1993

Atrial natriuretic factor in neonatal hypoxic-ischemic encephalopathy.

The influence of perinatal asphyxia in the secretion of atrial natriuretic factor (ANF) during the first 6 days of life, and its renal consequences are discussed. Comparison between 20 healthy term neonates and 19 with first--or second--degree hypoxic-ischemic encephalopathy (HIE) is made. Daily controls were performed on clinical and neurological examinations and administration of sodium and fluids. On the first and sixth days of life, 24 hours urine collection, natremia, natriuresis, fractionated excretion of sodium and creatinine clearance were determined. The ANF was performed at 1, 2, 3 and 6 days old, by R.I.A. The full term newborns with HIE showed a peak in ANF values on day two, as does the control group, thereafter maintaining higher levels, with a significant difference on day three and six. No correlation could be found between the ANF levels and the renal variables analyzed.

Asphyxia Neonatorum↗
PubMed1992

Inhibition of biliary lipid and protein secretion by cyclosporine A in the rat.

We investigated the effect of cyclosporine A (CyA) administered as a single i.v. dose of 20 and 40 mg/kg body wt, on biliary secretion of cholesterol, phospholipid, bile acid, and lysosomal marker and canalicular plasma membrane marker enzymes in anaesthetized Wistar rats. CyA reduced the concentration and biliary secretion of cholesterol, phospholipid and bile acid to a considerable extent; the inhibitory effect of CyA on the biliary secretion of phospholipid and bile acid was greater than that on cholesterol. The biliary outputs of acid phosphatase (AcP) and gamma-glutamyltransferase (gamma-GT) were also diminished by the drug, all these effects being dose-dependent. Maximum decreases in bile acid secretion were observed 10 min after administration, whereas those of cholesterol and phospholipid were delayed. Bile acid concentrations and secretion returned to pretest values at 30-50 min after CyA injection whereas those of cholesterol and phospholipid remained significantly reduced at this time point. The greater inhibitory effect of CyA on the biliary outputs of phospholipid and bile acid relative to cholesterol secretion together with the asynchronous fall and recovery of bile acid, cholesterol and phospholipid concentrations and secretion alter the cholesterol/bile acid, phospholipid/bile acid and cholesterol/phospholipid molar ratios as well as the lithogenic index, thus suggesting that CyA would uncouple biliary lipid secretion from bile acid secretion. Since under physiological conditions biliary lipid and gamma-GT secretion is related to and dependent upon bile acid secretion, we propose that the CyA-induced inhibition on lipid and gamma-GT secretion is, at least partly, secondary to the fall in bile acid output caused by the drug. However, since CyA inhibits secretory processes independent of the hepatobiliary flux of bile acid, such as the exocytic discharge of AcP, and because it also uncouples biliary lipid from bile acid secretion, other mechanisms and factors involved in lipid and protein secretion (such as intracellular transport, canalicular membrane fluidity and/or intracanalicular events) might also be altered by this drug.

Animals↗
PubMed1992

Increased expression of natural-killer-associated and activation antigens in multiple myeloma.

The expression of both natural-killer (NK)-associated and activation antigens was studied by flow cytometry in the peripheral blood of 47 untreated multiple myeloma (MM) patients. A significant increase in both absolute and relative numbers of CD57 positive cells as well as in the proportion of CD16 and CD11b cells was observed in patients with MM, specially in those in early stages of the disease (clinical stages I and II), suggesting a possible surveillance mechanism in response to an emerging malignant clone. Additional double stainings showed that strong CD16+ NK cells coexpress the CD56, CD11b, and CD2 antigens, while they lacked CD3, CD5, and WT31 antigens. Moreover, the previously reported increase in CD8 cells present in MM would be mainly due to a subset of CD8 cells that coexpress the CD57 Ags. The expression of activation antigens, especially CD38, was increased in peripheral blood lymphocytes of MM patients, the differences reaching statistical significance both in absolute and relative numbers in those cases with high numbers of CD16 NK cells and thus suggesting that these cells are functionally activated. These results reveal the existence of an increase in NK and activated cells in the peripheral blood of myeloma patients that may reflect a host's immunological mechanism in an attempt to modulate tumor cell growth.

ADP-ribosyl Cyclase↗
PubMed1992

[Tamoxifen as the primary treatment for breast cancer in elderly patients].

A total of 21 elderly patients with breast carcinoma without evidence of systemic dissemination received tamoxifen (20 mg daily) as primary treatment. Of these 57% had a potentially operable tumor (stages I:2, IIa:6, IIb:2, IIIa:2) with a high operative risk that contraindicated the surgery and 43% had a locally advanced tumor unfit for primary radiotherapy, chemotherapy, or surgery. The mean age was 81.3 +/- 5.7 years (range 70-91). Diagnosis was made by fine-needle aspiration cytology in 16 patients and by incision biopsy in 5 of them. The median follow-up was 11.5 months (range 3-54). In 67% there was a clinical objective response (RC: 14%, RP: 53%), and 33% had disease stabilization. There was no evidence of systemic dissemination during the follow-up. Two patients who had achieved a partial response with a duration of 11 and 54 months, respectively, had a loco regional progress. One of them responded to a second hormonal treatment. Of the patients, 81% are still alive, and 14% died of other causes. One patient was lost during the follow-up. These preliminary results show a high loco regional response to tamoxifen. A higher number of patients and a longer time of follow-up are needed to establish the habitual use of tamoxifen as primary treatment of breast carcinoma in elderly patients.

Aged↗
PubMed1991

Inhibition of biliary cholesterol and phospholipid secretion by cefmetazole. The role of vesicular transport and of canalicular events.

A number of organic anions selectively inhibit the biliary secretion of cholesterol and phospholipids without affecting bile acid secretion. We studied the effect of cefmetazole, a third-generation cephalosporin, on biliary lipid secretion in the rat. Injection of cefmetazole at a dose of 200 mumol/kg body wt. induced a choleretic effect and a significant decrease in the biliary output of cholesterol and phospholipid, without changes in bile acid secretion. The decrease was more marked for cholesterol than for phospholipid secretion, with a significant decrease in their molar ratio in bile. The effects were apparently unrelated to an inhibition of intracellular vesicular transport because, after injection of horseradish peroxidase, both the time course and total amount secreted of the protein did not significantly differ between control animals and those receiving cefmetazole. The secretory rate of the lysosomal marker acid phosphatase was not affected by cefmetazole administration. Biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma-glutamyltransferase were significantly decreased by the antibiotic. These results point to an effect of cefmetazole at the level of the canalicular membrane.

Alkaline Phosphatase↗
PubMed1991

Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease. Castellano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies.

In 112 untreated myeloma patients we have analysed the immunophenotype of plasma cells both by immunofluorescence (IF) and immunocytochemistry (APAAP). Both techniques yielded similar results pointing to an important degree of heterogeneity in antigenic expression not only between different patients but also within the same patient. The expression of CD38 and Han-PC1 antigens (Ags) was almost constant (greater than 90% positive cases), while CD9 was detected in 66% of the cases. On the other hand, less than one third of patients were positive for CD10, CD20 and HLA-DR and generally with a weak expression (less than 30% positive plasma cells). In occasional cases plasma cells were weakly positive for the myelomonocytic markers CD13 (9%), CD15 (25%) and CD14 (6%). The possibility that this heterogeneity might be the result of different stages of differentiation of the neoplastic clone is suggested both by the positive correlation in the expression of some of these antigens (CD10, CD9, CD20, HLA-DR) and by the relationship between CD10 and myeloid antigens with immature plasma cell morphology. Finally, the cALLA antigen does not seem to be of significant value in predicting survival. Moreover, none of the other markers explored showed a clear influence in the course of the disease, although the tendency towards a lower survival found for the CD20+ cases as well as the association of the expression of some antigens and advanced clinical stage, may warrant further studies in a larger series of patients.

Aged↗
PubMed1991

Impairment of maximal bilirubin secretion by cyclosporin A in the rat.

The effect of cyclosporin A on the maximal secretion of bilirubin was investigated in male Wistar rats. Following a saturating load of the pigment, intravenous administration of cyclosporin A as a single bolus (20 mg/kg) significantly reduced bile flow and bile acid secretion. The bilirubin secretory transport maximum was alos significantly reduced. The decreased excretion of the bile pigment corresponded both to bilirubin mono- and di-conjugates, the excretion of unconjugated bilirubin being slightly and non-significantly reduced. Plasma and liver bilirubin concentrations were significantly increased, while liver UDP-glucuronosyltransferase activity did not significantly differ between control and cyclosporin A-treated rats. Our data indicate that, although in cyclosporin A-treated rats there are no changes in the activities of others markers of hepatocellular dysfunction, the overall plasma to bile transfer of bilirubin is altered. The reduced hepatobiliary transport of the pigment is mainly caused by an impairment of its intracellular/canalicular transport.

Animals↗
PubMed1990

Alteration of purine metabolism by AICA-riboside in human B lymphoblasts.

The effect of 5-amino-4-imidazole-carboximide (AI-CA)-riboside on different pathways of purine metabolism (biosynthesis de novo, salvage pathways, adenosine metabolism, ATP catabolism) was studied in human B lymphoblasts (WI-L2). AICA-Riboside markedly decreased intracellular levels of 5-phosphoribosyl-1-pyrophosphate and in consequence affected purine biosynthesis de novo and purine salvage pathways. AICA-riboside inhibited incorporation of glycine into purine nucleotides, but when formate was used as the precursor of purine biosynthesis de novo, a biphasic effect was observed. The incorporation of formate into purine nucleotides was increased by AICA-riboside at concentrations up to 2 mM but decreased at higher concentrations. Salvage of the purine bases adenine, hypoxanthine, and guanine was markedly inhibited and utilization of extracellular adenosine in B lymphoblasts was reduced by AICA-riboside. AICA-riboside increased ribose 1-phosphate concentrations and increased degradation of prelabeled ATP. No effect on the intracellular levels of orthophosphate was found. Proliferation of WI-L2 lymphoblasts was only slightly affected at concentrations of AICA-riboside below 500 microM but markedly inhibited by higher concentrations.

Adenosine↗
PubMed1990

Selective adenosine release from human B but not T lymphoid cell line.

Intracellular adenosine formation and release to extracellular space was studied in WI-L2-B and SupT1-T lymphoblasts under conditions which induce or do not induce ATP catabolism. Under induced conditions, B lymphoblasts but not T lymphoblasts, release significant amounts of adenosine, which are markedly elevated by adenosine deaminase inhibitors. In T lymphoblasts, under induced conditions, only simultaneous inhibition of both adenosine deaminase activity and adenosine kinase activities resulted in small amounts of adenosine release. Under noninduced conditions, neither B nor T lymphoblasts release adenosine, even in the presence of both adenosine deaminase or adenosine kinase inhibitors. Comparison of B and T cell's enzyme activities involved in adenosine metabolism showed similar activity of AMP deaminase, but the activities of AMP-5'-nucleotidase, adenosine kinase and adenosine deaminase differ significantly. B lymphoblasts release adenosine because of their combination of enzyme activities which produce or utilize adenosine (high AMP-5'-nucleotidase and relatively low adenosine kinase and adenosine deaminase activities). Accelerated ATP degradation in B lymphoblasts proceeds not only via AMP deamination, but also via AMP dephosphorylation into adenosine but its less efficient intracellular utilization results in the release of adenosine from these cells. In contrast, T lymphoblasts release far less adenosine, because they contain relatively low AMP-5'-nucleotidase and high adenosine kinase and adenosine deaminase activities. In T lymphoblasts, AMP formed during ATP degradation is not readily dephosphorylated to adenosine but mainly deaminated to IMP by AMP deaminase. Any adenosine formed intracellularly in T lymphoblasts is likely to be efficiently salvaged back to AMP by an active adenosine kinase. In general, these results may suggest that adenosine can be produced only by selective cells (adenosine producers) whereas other cells with enzyme combination similar to SupT1-T lymphoblasts can not produce significant amounts of adenosine even in stress conditions.

Adenosine↗
PubMed1990

Effects of ursodeoxycholate on maximal biliary secretion of bilirubin in the rat.

The effect of sodium ursodeoxycholate (0.5 and 1.0 mumol/min/100 g) on the maximal biliary secretion (Tm) of bilirubin and on the concentration of bilirubin in liver and plasma at the end of a bilirubin load was studied in Wistar rats. Administration of ursodeoxycholate at 0.5 mumol/min/100 g caused a 0.8-fold increase in bile flow and a significant increase in the bilirubin Tm (+24%). This was associated with a significant reduction of liver and plasma bilirubin concentrations (-16% and -17%, respectively). Bilirubin UDP-glucuronosyltransferase activity was not significantly enhanced. There was a significant increase in the biliary excretion of bilirubin conjugates (+30%) and in the diconjugates/monoconjugates ratio in bile (+31%). When ursodeoxycholate was given at 1.0 mumol/min/100 g, it produced a 1.7-fold increase in bile flow, but the bilirubin Tm was significantly reduced (-21%). Liver bilirubin concentrations were decreased (-20%) and there was a significant enhancement in total pigment concentration in plasma (+19%). Both the excretion of unconjugated bilirubin and that of bilirubin conjugates were significantly reduced (-60% and -18%, respectively). There was a significant decrease in the bilirubin-UDP glucuronosyltransferase activity and the diconjugates/monoconjugates ratio in bile (-27% and -27%, respectively). These results indicate that ursodeoxycholate is able to increase maximal bilirubin secretion only when administered at low doses and that infusion at higher rates can significantly interfere with different steps in the hepatobiliary transport of the pigment.

Animals↗
PubMed1990

Choleretic mechanism and effects of cyclobutyrol in the rat: dose-response relationship.

Although there is general agreement on the hydrocholeretic properties of the so-called "synthetic choleretics" on biliary secretion, related simply to the kinetics of excretion, recent studies suggest that some of these drugs also have a pharmacodynamic effect; mainly, stimulation of bile acid secretion. In the present work, we studied the biliary response to different doses of cyclobutyrol (CB) in order to determine whether this agent stimulates the secretion of bile acids and to establish the relationships between dose and the choleretic effects in anaesthetized rats. Biliary bile flow, sodium, potassium, chloride and bicarbonate outputs were found to be increased and bile acid concentrations reduced in a dose-dependent fashion after 0.40, 0.54, 0.80, 1.08 and 2.16 mmol/kg b.wt. of CB administration. All assayed doses had no effect on the bile acids secretion rate. These findings suggest that a) CB-induced choleresis is unrelated to bile acids; b) CB and bile acids do not compete for the hepatobiliar transport mechanisms, despite the anionic character of both compounds, and c) in the rat the active mechanisms involved in the biliary elimination of CB are not saturated even at the large doses employed.

Administration, Oral↗
PubMed1989

Inhibition of biliary cholesterol and phospholipid secretion during cyclobutyrol-induced hydrocholeresis.

The effects of sodium cyclobutyrate, a synthetic hydrocholeretic drug, on biliary lipid secretion and on the biliary outputs of several plasma-membrane enzymes were investigated in anaesthetized rats. Administration of a single oral dose of cyclobutyrol (0.72 mmol/kg body wt.) reduced biliary concentration and output of cholesterol and phospholipid. However, bile acid secretion was not significantly modified. This uncoupling effect of lipid secretion remained even when the choleretic response to the drug had ceased. It additionally led to a statistically significant decrease in the cholesterol/bile acid and phospholipid/bile acid molar ratios and in the lithogenic index of the bile. The biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma-glutamyltransferase were markedly reduced by the drug. When cyclobutyrol was administered to rats which had been previously fed with a high-cholesterol diet, the effects of cyclobutyrol persisted, but were less marked. Our results demonstrate that the bile acid-independent choleresis induced by cyclobutyrol (related to its pharmacokinetic effect) is accompanied by a pharmacodynamic action that selectively reduces the secretion of biliary lipids. This is due to an uncoupling of the secretion of cholesterol and phospholipids from that of bile acids. Possible explanations for the biliary response to cyclobutyrol are discussed.

Alkaline Phosphatase↗
PubMed1989

Cholestasis in the rat by means of intravenous administration of cyclosporine vehicle, Cremophor EL.

The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. The Cremophor EL-induced cholestasis was an immediate and reversible phenomenon, since at 30-35 min after drug injection all parameters evaluated had returned to control values. A slight increase in serum bilirubin concentrations was observed. Our data indicate that the observed cholestasis is related to a reduction in both bile acid-dependent and bile acid-independent bile flow, probably due to a transitory hepatotoxic effect of Cremophor EL. We conclude that the clinically used vehicle for i.v. administration of cyclosporine, Cremophor EL, has adverse effects on hepatobiliary physiology in the rat and suggest that an alternative vehicle should be used.

Animals↗
PubMed1989

Biliary excretion and choleretic effect of cefmetazole in rats.

The effect of cefmetazole, a broad-spectrum cephalosporin, on bile flow and composition in rats was studied. Intravenous injection of cefmetazole at doses ranging from 40 to 400 mumol/kg of body weight led to an increase in its biliary concentration and excretion rate, with a maximum at 30 min after injection. Excretion of cefmetazole into bile was associated with a marked choleresis. The magnitude of the increase in bile flow was dose dependent, with a maximal increase at a dose of 200 mumol/kg. Cefmetazole administration did not affect the secretion of bile acids or their osmotic activities, whereas the bile acid-independent bile flow increased by 49% at a dose of 200 mumol/kg. Cefmetazole administration at a dose of 200 mumol/kg significantly increased the biliary outputs of sodium, potassium, chloride, and bicarbonate (+36, +56, +28, and +31%, respectively) compared with outputs of controls. A linear relationship was observed between bile flow and cefmetazole excretion, 44 microliters of bile being produced per mumol of cefmetazole excreted into bile. Our results demonstrate that cefmetazole induces choleresis by stimulating bile acid-independent bile flow. This effect appears to be partly due to the osmotic properties of cefmetazole transported into bile.

Animals↗