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Biomedical subjects

J Ortuño

Publications and source records attributed to J Ortuño.

At least 19 recordsLinked to original sources
PubMed2001

Outcome of cadaveric renal transplant patients treated for 10 years with cyclosporine: is chronic allograft nephropathy the major cause of late graft loss?

BACKGROUND: The introduction of cyclosporine (CsA) has improved the short-term outcome of renal transplantation, but its effect on the long-term survival is not well known. METHODS: We analyzed 128 cadaveric first renal transplant recipients with CsA and prednisone as basal immunosuppression followed for at least 10 years, and we have compared them with a group of 185 historical patients treated with azathioprine (Aza) and prednisone. RESULTS: The 1-year graft survival was 83% in the CsA-treated patients and 68% in the Aza-treated patients (P<0.025), and the differences were significant for 3 years. Acute rejection accounted for the 10.9% of losses in CsA-treated patients and for 23.8% of losses in Aza-treated patients (P=0.046). Chronic allograft nephropathy was the cause of graft losses in 40.6% and 16.8% of cases (P=0.008). Patient survival at 5 years was 88% in CsA-treated patients and 79% in the Aza-treated patients (P<0.025). When analyzing the data of the 64 CsA-treated patients and the 84 Aza-treated patients with one functioning graft at 10 years, mean serum creatinine values were significantly higher in the CsA-treated patients at all time points but the increases were not significantly different. At 10 years, mean blood pressure was higher (P=0.002), and hypercholesterolemia (P=0.011) and hyperuricemia (P=0.000) were more prevalent in the CsA-treated patients. CONCLUSIONS: CsA resulted in a better short-time patient and graft survival that was not maintained in the long-term outcome. Chronic allograft nephropathy was the leading cause of graft loss in CsA-treated patients. Graft function was poorer in the CsA-treated patients, but its decline was similar in the two groups.

Adult↗
PubMed2001

Effect of oral administration of high vitamin C and E dosages on the gilthead seabream (Sparus aurata L.) innate immune system.

The effect of the oral administration of high dosages of vitamins C and E on the innate immune system of the seabream was investigated. Gilthead seabream (Sparus aurata L.) were fed four different diets for 45 days: a commercial diet as control, a 3g/kg vitamin C-supplemented diet, a 1.2g/kg vitamin E-supplemented diet or a diet containing both vitamin supplements. After 15, 30 and 45 days, serum ascorbic acid and alpha-tocopherol levels, growth, complement titers and head-kidney leucocyte phagocytic and respiratory burst activities were evaluated. The results showed that serum vitamin levels reflected dietary input. Fish fed the vitamin C-supplemented diet showed an enhanced respiratory burst activity, while fish fed the vitamin E-supplemented diet exhibited increased complement and phagocytic activities. All of these positive effects were found in fish fed the joint diet, as well as a synergistically enhanced respiratory burst activity at day 30. The results demonstrate that in vivo vitamins C and E exert a synergistic effect enhancing the respiratory burst activity of seabream phagocytes.

Administration, Oral↗
PubMed2001

Effects of short-term crowding stress on the gilthead seabream (Sparus aurata L) innate immune response.

Gilthead seabream specimens were subjected to an intense short-term crowding stress of 100 kg m(-3) for 2 h. After 0, 1, 2, 3 and 4 days, blood glucose and serum cortisol levels, serum complement activity, phagocytic and respiratory burst activities of head-kidney leucocytes, and the percentage of monocyte/ macrophages and granulocytes in head-kidney and circulating blood were determined. An immediate effect of the stress was a depression in complement and phagocytic activities, both of which recovered after 3 or 2 days, respectively, while respiratory burst remained unaffected. The depression of phagocytosis in head-kidney leucocytes seemed to correlate with stress-induced migration of active cells from the organ to circulating blood. The present results point to the importance of minimising intense short-term crowding stress in order to reduce possible states of immunodepression in farmed fish.

Animals↗
PubMed2001

Immunomodulatory effects of dietary intake of chitin on gilthead seabream (Sparus aurata L.) innate immune system.

To determine the effects of chitin (poly [1-->4]-beta-N-acetyl-D-glucosamine) on the innate immune response of gilthead seabream (Sparus aurata L.), fish were fed diets containing 0 mg (control), 25, 50 or 100 mg kg(-1) chitin for 2, 4 and 6 weeks. Lysozyme and natural haemolytic complement activities, together with head-kidney leucocyte respiratory burst, phagocytic and cytotoxic activities, were studied at each of the assayed times. Lysozyme activity was unaffected by the administration of chitin. The innate humoral and cellular immune response activities assayed were enhanced by the dietary intake of chitin, each increasing at a different time: natural haemolytic complement activity and cytotoxic activity after 2 weeks of treatment, respiratory burst activity from 4 weeks and phagocytic activity after 6 weeks, although, unlike the other activities, no statistically significant differences were observed in the first. The results indicate that chitin increases the activity of the seabream innate immune system, and its use as an immunostimulant is discussed, especially with regards to the protective role.

Animals↗
PubMed2001

Vitamin E increases natural cytotoxic activity in seabream (Sparus aurata L.).

The natural cytotoxic activity of head-kidney leucocytes from gilthead seabream (Sparus aurata L.), after in vitro and in vivo vitamin E treatment, against tumor cells was studied by flow cytometry. Leucocytes were incubated in culture medium with different vitamin E supplementations (0.01-10 microg ml(-1)) for 6, 24 or 48 h and the results demonstrate that all the assayed vitamin E supplementations significantly enhanced the natural cytotoxic activity of leucocytes. To determine the effect of a high dietary level of vitamin E on this activity, fish were fed with 0 (control), 600, 1200 or 1800 mg of vitamin E supplementation kg(-1) diet for 2, 4 or 6 weeks. After 2 and 4 weeks of treatment, the natural cytotoxic activity was significantly enhanced at the highest (1.8 g kg(-1) diet) and lowest (600 mg kg(-1) diet) vitamin E supplement dosage, respectively. No effect of the vitamin E supplemented diet on seabream leucocyte natural cytotoxic cell activity was observed after 6 weeks of treatment.

Animals↗
PubMed2001

Sweat testing of MDMA with the Drugwipe analytical device: a controlled study with two volunteers.

Rapid on-site tests for the analysis of drugs of abuse in unconventional specimens (e.g., sweat) have recently been developed. Two healthy volunteers familiar with the effects of methylenedioxymethamphetamine (MDMA) were given 100 mg of the drug as a single oral dose. MDMA and its main metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) were determined in plasma and urine by gas chromatography-mass spectrometry (GC-MS). MDMA was also investigated in sweat with the Drugwipe (an immunochemical strip test). Subjects' armpits were swabbed for 10 s at 0 time (predose) and at 2, 6, 8, 12, and 24 h after MDMA administration. MDMA consumption could be detected using Drugwipe at 2 h and for as long as 12 h after drug administration. However, in one of the volunteers, a faint color change appeared at 0 time, when plasma and urine tested negative for MDMA and did not disappear even 48 h later. Plasma concentrations of MDMA and HMMA measured by GC-MS peaked at 2-4 h, and values greater than 20 ng/mL for MDMA and of 40 ng/mL for HMMA were still detected at 24 h. Urine tested positive by GC-MS for MDMA and HMMA in the 48-h collection period. These findings preliminarily support sweat testing with Drugwipe for monitoring MDMA use.

Humans↗
PubMed2001

Prognosis of patients with acute renal failure without cardiopathy.

BACKGROUND: The outcome for children with acute renal failure (ARF) may be poor. However, relatively few published studies have considered prognosis of these patients. METHODS: We prospectively studied, from 1978 to 1998, 92 such children without heart disease to try to identify risk factors for mortality. RESULTS: Forty five per cent of children with tumours, shock, and other causes died compared with none of those with a primary urinary tract related problem. ARF did not seem to be the cause of death in any case. Univariate analysis showed that in the non-primary urinary problem group (55 cases), patients with hypotension, high values of BUN or creatinine, or who needed mechanical ventilation or dialysis, had a poor outcome. Multivariate analysis showed that probability of death can be estimated using the following score: -0.02 + 0.28 (hypotension) + 0.19 (ventilation) + 0.27 (dialysis) + 0.01 (BUN). CONCLUSIONS: Mortality of patients with ARF was related to aetiology, the need for dialysis and/or ventilator use, hypotension, and BUN values.

Acute Kidney Injury↗
PubMed2001

Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans.

Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested. Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stimulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-beta and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-gamma) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status.

Adult↗
PubMed2000

Derivatization procedures for the detection of beta(2)-agonists by gas chromatographic/mass spectrometric analysis.

An evaluation of derivatization procedures for the detection of beta(2)-agonists is presented. The study was performed with the beta(2)-agonists bambuterol, clenbuterol, fenoterol, formoterol, salbutamol, salmeterol and terbutaline. Different derivatizating agents were employed, aiming to obtain derivatives with high selectivity to be used in the gas chromatographic/mass spectrometric analysis of beta(2)-agonists in biological samples. Trimethylsilylation was compared with different agents and the role of some catalysts was evaluated. Acylation, combined trimethylsilylation and acylation, and the formation of cyclic methylboronates were also studied. Sterical hindrance caused by different substituents at the nitrogen atom of the beta-ethanolamine lateral chain of beta(2)-agonist molecules is mainly responsible for differences in the abundances of the derivatives obtained. The use of catalysts produces an increase in the derivatization yield, especially for compounds with low steric hindrance (substituents with primary and secondary carbon atoms). The formation of trimethylsilyl (TMS) ethers is not influenced by structural molecular differences when only hydroxy groups are involved in derivatization. Combined trimethylsilylation and acylation showed that compounds with a secondary carbon atom linked to the nitrogen atom form mainly N-TFA-O-TMS derivatives, with a small amount of N-TMS-O-TMS derivatives. Compounds with tert-butyl substituents at the amino group (bambuterol, salbutamol and terbutaline) formed O-TMS derivatives as the main products, although a limited amount of trifluoroacylation at the nitrogen atom also occurred. Cyclic methylboronates were formed with bambuterol, clenbuterol, formoterol, salbutamol and salmeterol. Owing to hydroxy substituents in unsuitable positions for ring formation, this procedure was not effective for fenoterol and terbutaline. Mass spectra of different derivatives and tentative fragmentation profiles are also shown. For screening purpose (e.g. sports drug testing), derivatization with MSTFA or BSTFA alone is recommended as a comprehensive derivatization technique for beta(2)-agonists owing to minimal by-product formation; formation of cyclic methylboronates can be useful for confirmation purposes. Detection limits were obtained for the TMS and cyclic methylboronate derivatives using the derivatizing reagents MSTFA and trimethylboroxine, respectively. For most of the compounds, lower detection limits were found for the TMS derivatives.

Acetamides↗
PubMed2000

High dietary intake of alpha-tocopherol acetate enhances the non-specific immune response of gilthead seabream (Sparus aurata L.).

To determine the effects of three high levels of dietary intake of alpha-tocopherol acetate (vitamin E) on the non-specific immune response of gilthead seabream (Sparus aurata L.), specimens were fed a commercial diet (100 mg alpha-tocopherol kg-1) as control, or vitamin E supplemented diets (600, 1200 or 1800 mg alpha-tocopherol acetate kg-1) for 15, 30 or 45 days. Growth, serum alpha-tocopherol levels, natural haemolytic complement activity and head-kidney leucocyte migratory, respiratory burst and phagocytic activities were studied at each of the assay times. A positive correlation between alpha-tocopherol acetate intake and serum alpha-tocopherol levels was observed, the increase being linked to both the dosage and length of treatment. Specimens fed the diet supplemented with 600 mg vitamin E kg-1 showed no enhancement in any of their immune parameters, while those fed the diet supplemented with 1200 mg vitamin E kg-1 presented a slightly higher (but not statistically significant) specific growth rate than fish fed the other diets. In addition, serum haemolytic activity and the phagocytosis of head-kidney leucocytes were enhanced by the dietary intake of 1200 mg vitamin E kg-1 after 30 and 45 days of treatment, although leucocyte migration and respiratory burst activity remained unaffected. The highest vitamin E dietary dose used, 1800 mg kg-1, unexpectedly provoked no immunostimulation. These results indicate that a moderate level of vitamin E in the diet (1200 mg kg-1) stimulates the seabream's non-specific immune system after 30 days of administration. Lower or higher vitamin E concentrations may not be so effective, because of an imbalance in the vitamin E ratio with other antioxidants. The proposed dietary levels of vitamin together with the indicated administration time could be useful for reducing the susceptibility of farmed fish to infectious diseases.

Animals↗
PubMed2000

Effects of injecting chitin particles on the innate immune response of gilthead seabream (Sparus aurata L.).

To determine the effects of chitin (poly [1-->4]-beta-N-acetyl-D--glucosamine) particles on the innate immune response of gilthead seabream (Sparus aurata L.), specimens were injected intravenously or intraperitoneally with the substance. Natural haemolytic complement activity, head-kidney leucocyte respiratory burst activity and phagocytic and cytotoxic activities were analysed in vitro 3, 5 or 10 days post-injection. All the immune parameters assayed remained unaffected when chitin was intravenously administered. However, the fish that had been intraperitoneally injected showed increased humoral and cellular immune responses. Natural haemolytic complement activity increased from 5 days post-injection although no statistically significant differences were observed. Respiratory burst and phagocytic activities peaked at 3 and 5 days post-injection, respectively, while cytotoxic activity had increased by 3 days post-injection and remained high until 10 days post-injection.

Animals↗
PubMed2000

Tacrolimus is highly effective in both dual and triple therapy regimens following renal transplantation. Spanish and Italian Tacrolimus Study Group.

This open, multicenter, randomized, parallel-group study evaluated the efficacy and safety of tacrolimus-based dual and triple therapy regimens. For this 3-month study (with 12-month follow up), 491 adult renal transplant patients were randomized and received either dual therapy (tacrolimus/corticosteroids; 246 patients) or triple therapy (tacrolimus/corticosteroids/azathioprine; 245 patients). Patient survival rates at months 3 and 12 were 99.2 (dual) vs 99.6% (triple) and 97.8 vs 98.7%, respectively. Graft survival rates at months 3 and 12 were 94.1 (dual) vs 95.4% (triple) and 92.8 vs 93.3%, respectively. After 3 months, the incidences of treated acute rejection were 28.8 (dual) and 29.7% (triple); and 7.6 (dual) and 5.4% (triple) for corticosteroid-resistant acute rejections. Between months 4 and 12, three new first rejections were reported, (dual: 2, triple: 1). For leukopenia (1.3 vs 11.7%; P < 0.001) and anemia (14.8 vs 23.0%, P = 0.026), significantly higher incidences were reported in the triple therapy group. The incidence of de novo insulin-dependent diabetes was 5.6 (dual) and 4.0% (triple) at month 3. In terms of efficacy, no difference between the treatment groups was observed.

Acute Disease↗
PubMed2000

Non-linear pharmacokinetics of MDMA ('ecstasy') in humans.

AIMS: 3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers. METHODS: A total of 14 subjects were included. In the pilot phase six received MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6 activity and were classified as extensive metabolizers for substrates, such as MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine samples were collected throughout the study for the evaluation of MDMA pharmacokinetics. Body fluids were analysed for the determination of MDMA and its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy-amphetamine (HMA). RESULTS: As the dose of MDMA administered was increased, volunteers showed rises in MDMA concentrations that did not follow the same proportionality which could be indicative of nonlinearity. In the full range of doses tested the constant recovery of HMMA in the urine combined with the increasing MDMA recovery seems to point towards a saturation or an inhibition of MDMA metabolism (the demethylenation step). These observations are further supported by the fact that urinary clearance was rather constant while nonrenal clearance was dose dependent. CONCLUSIONS: It has previously been postulated that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10% of the Caucasian people) were at risk of developing acute toxicity at moderate doses of MDMA because the drug would accumulate in the body instead of being metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype. It implies that relatively small increases in the dose of MDMA ingested are translated to disproportionate rises in MDMA plasma concentrations and hence subjects are more prone to develop acute toxicity.

3,4-Methylenedioxyamphetamine↗
PubMed2000

Antiproteinuric effect of calcium antagonists on puromycin-induced experimental nephrosis.

Calcium antagonists have a potential for beneficial effects on kidney function unrelated to their antihypertensive action. In this study we have investigated the efficacy of calcium antagonists compounds (verapamil, nifedipine and diltiazem) on reversible acute renal insufficiency, proteinuria and interstitial nephritis induced by the puromycin ammonucleoside (PAN). An increase in blood pressure (BP) was detected on day 14, with no statistical differences in the response to calcium antagonists. Serum creatinine concentration increased to 1.2 mg/dL on day 7 after PAN and decreased to 0.7 mg/dL at 14 days, calcium antagonists shortened the time required to reach baseline or control levels. Calcium antagonists also reduced proteinuria in the PAN-treated animals, in both day 7 and day 14. Differential effects of the antagonists were observed. Verapamil caused a greater reduction (p < 0.01) in proteinuria than nifedipine or diltiazem in day 7. Moreover, verapamil (p < 0.01) and nifedipine (p < 0.01) reduced the total number of interstitial infiltrating leukocytes from 690 to 120 and 425 positive cells/20 high power fields (x63) respectively, by contrast, diltiazem had no effect. We conclude that in this model of PAN nephropathy verapamil is more effective in reducing both proteinuria and the severity of acute interstitial nephritis than either nifedipine or diltiazem. The possible clinical implications of these results remain to be elucidated.

Animals↗
PubMed2000

Immunomodulating activity of MDMA.

MDMA (3,4-methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a "chemical stressor." It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a modulation of several immune functional parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produced a rapid and sustained suppression of induced lymphocytes proliferation and a significant decrease in circulating lymphocytes. These alterations in rat immune function were accompanied by a significant rapid increase in plasma corticosterone concentrations. It was postulated that the result of altered induced proliferation response of lymphocytes could have been due to a combined effect of direct action of MDMA on lymphocytes and to the activation of the hypothalamic pituitary adrenal axis (HPA axis) and/or the sympathetic nervous system (SNS) via central mechanisms. In humans, acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in CD4+ T-cells and functional responsiveness of lymphocytes to mitogenic stimulation, while percentage of natural killer cells significantly increased. A rise of cortisol plasma concentrations similar to that observed in the rat model supported the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the median eminence of the hypothalamus and subsequent HPA axis and SNS activation. The present findings indicate that MDMA ingestion may represent a potential health hazard for an increased risk of immune system-related diseases.

Animals↗