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Biomedical subjects

A Gimeno

Publications and source records attributed to A Gimeno.

At least 19 recordsLinked to original sources

Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling.

Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARalpha, RARbeta, RARgamma, and RXRalpha, which underwent an increase in protein levels during weaning. In an attempt to elucidate the RARalpha-dependent signaling pathway, ChIP assays were performed. The results showed the binding of RARalpha to the MMP-9 promoter after 24- and 72-h weaning together with its coactivator p300; this fact could be responsible for the increase found in MMP-9 mRNA and protein levels in these conditions. Expression of related MMPs (MMP-2 and MMP-3) was also increased during weaning. Using gelatine zymography, we observed a time-dependent increase in active forms of MMP-9 and MMP-2. On the other hand, the inhibitor of MMPs, TIMP-1, was almost undetectable at 24- and 72-h weaning by Western blot. The role of retinoids in matrix remodeling is reinforced by the fact that administration of an acute dose of retinol palmitate to control lactating rats also induces MMP-9 expression. This emphasizes the importance of retinoids in vivo to regulate mammary gland involution.

Adipogenesis↗

Modulation of hepatocyte growth factor plasma levels in relation to the dose of exogenous heparin administered: an experimental study in rats.

INTRODUCTION: Partial liver transplantation has been consolidated to be a valid treatment option. We sought to understand the factors that modulate and may be harnessed to accelerate hepatocyte regeneration. We sought to determine the impact of heparin on m-hepatocyte growth factor (HGF) plasma concentrations. MATERIALS AND METHODS: Sixteen rats were assigned to four groups of four animals each: group A, without heparin; group B, 600 IU/kg; group C, 1000 IU/kg, group D, 1400 IU/kg. Blood samples (0.5 mL) were obtained from each rat at baseline and at 30, 60, 120, and 240 minutes. After the samples were centrifuged to separate supernates from the cell phase they were stored at -20 degrees C in the m-HGF reagent and subsequently tested using enzyme-linked immunosorbent assay. Results were analyzed using SPSS 11.5 statistical software. RESULTS: Among the 16 rats, one died at 110 minutes, just prior to the last extraction. The remaining rats were sacrificed. Mean weight was: 466 +/- 64.24 g with no intergroup differences (P = .149). The comparative results (using Student t test) were: baseline A(1-4) versus A(1-4) 30 minutes: P < .05; baseline A(1-4) versus A(1-4) 60 minutes: P < .05; baseline A(1-4) versus A(1-4) 120 minutes: P = .10 (NS); baseline A(1-4) versus A(1-4) 240 minutes: P = .15 (NS). No significant differences were found among group B: baseline C(1-4) versus C(1-4) 30 minutes and 60 minutes: NS; baseline C(1-4) versus C(1-4) 120 minutes: P < .001; baseline C(1-4) versus C(1-4) 240 minutes: P < .10 (NS). Finally, the results in group D were: baseline D(1-4) versus D(1-4) 30 minutes: NS; baseline D(1-4) versus D(1-4) 60 minutes and 120 minutes: P < .05; baseline D(1-4) versus D(1-4) 240 minutes: P < .0005. When we compared group A to C and D, we detected differences (albeit not when compared to B) with P values = .01. Peak values were obtained at 120 and 240 minutes (225.21 pg/mL and 221.78 pg/mL) among groups C and D. CONCLUSION: Heparin has a positive effect to increase serum HGF concentrations among rats. The effect was dependent on the administered dose and the time elapsed.

Animals↗

Simultaneous liver-kidney transplantation for adult recipients with irreversible end-stage renal disease.

HYPOTHESIS: Combined liver-kidney transplantation is safe (low morbidity and acceptable mortality) and effective in patients with end-stage liver disease. Although refinements in surgical technique have resulted in better patient and allograft outcomes, the negative impact of renal insufficiency on survival in patients undergoing liver transplantation has been widely reported, although some aspects are controversial. DESIGN: Analysis of the clinical characteristics and outcome in the management of patients undergoing combined liver-kidney transplantation. The end points were operative mortality, morbidity, and long-term survival. SETTING: University Hospital 12 de Octubre. PATIENTS: Between May 1986 and December 2001, 820 liver transplantations were performed. There were 16 cases (1.96%) of combined liver-kidney transplantations, which represent the sample of this study. RESULTS: Mean +/- SD follow-up of 42.2 +/- 29 months: 6 patients died (37.5% mortality rate). There were 4 (25%) hospital deaths within 6 months following surgery and 2 after 6 months (4 sepsis, 1 refractory heart failure, and 1 recurrent hepatitis C virus disease). Univariate analysis related to mortality included age, sex, etiology, preoperative creatinine level, United Network for Organ Sharing status, Child-Pugh score, type of hepatectomy (piggyback), intraoperative blood product administration, and the presence of postoperative complications. The only 2 significant factors were the presence of postoperative complications (P = .01) and the United Network for Organ Sharing status (P = .02). Crude survival rate was 62.5%. Actuarial survival rates were 80%, 71%, and 60% at 1, 3, and 5 years, respectively. CONCLUSION: Because end-stage renal disease is not a formal contraindication for liver transplantation, a combined liver-kidney transplantation for adults with end-stage renal disease can be done safely and effectively.

Adult↗

Study of the correlation between two methods used to monitor thymoglobulin therapy in renal transplantation.

The aim of this study is to evaluate the correlation between the 2 methods used to monitor thymoglobulin therapy: the total lymphocyte count and the number of T cells. We have performed daily collections of peripherical blood samples from 24 renal grafts, recipients who were receiving thymoglobulin, including 14 cases for induction and 10 for acute rejection. Absolute lymphocyte and T-cell counts were measured in the 298 samples after administration of a dose of 1.25 mg/kg/d. The dose was omitted if the T-cell count had decreased to <10 cells/microL. The theoretical total lymphocyte count considered to omit dose was <100 cells/microL. A total of 137 doses were given according to T-cell count. We performed the comparison in 3 steps. First, we correlated values in the daily samples; second, we examined samples as a whole and third, assessed the percentage of discrepancy between the omission of the daily dose according to each method. There was a poor correlation between the methods according to sets of daily samples or the sets as a whole. The rate of discrepancy was 66%, including 121 of 216 decisions (P<.001). In conclusion, the results of the 2 methods of monitoring thymoglobulin therapy are different, and the total administered dose depends on the method used.

Antilymphocyte Serum↗

Liver transplantation and transjugular intrahepatic portosystemic shunt.

OBJECTIVE: Describe the results of liver transplantation after installing Transjugular Intrahepatic Portosystemic Shunt (TIPS) and compare them with those of a control group in a comparative, longitudinal, retrospective study. MATERIALS AND METHODS: Between April 1986 and October 2002, we performed 875 liver transplantations. Between January 1996 and October 2002, 26 transplantations were performed on TIPS carriers. This group was compared with a control cohort of 50 randomly selected patients who underwent transplantation in this period (non-TIPS carriers). Both groups were homogeneous with no significant differences between age, sex United Network for Organ Sharing (UNOS) score, Child stage, or etiology. RESULTS: Actuarial survival rates at 1 and 3 years: TIPS group 96.15% and 89.29% versus control cohort 87.8% and 81%, respectively. In 73.9%, the TIPS was clearly effective; in 88.9%, a postoperative Doppler revealed normal flow. There were no statistically significant differences compared with time on the waiting list for transplant, duration of the operation, ischemia times, intraoperative consumption of hemoderivates, vascular or nonvascular postoperative complications, duration of stay in the intensive care unit, hospital stay, or retransplantation rate. CONCLUSIONS: In our experience, TIPS insertion does not affect either the intraoperative or postoperative evolution and is not associated with an increased time on the liver transplant waiting list.

Actuarial Analysis↗

Incidence of microflora and of ochratoxin A in green coffee beans (Coffea arabica).

Coffee is produced in tropical countries around the Equator where climatic conditions are favourable for fungal development and mycotoxin production; however, mycotoxins do not only occur in the tropical countries. The aim was to evaluate the mycoflora and possible incidence of ochratoxin A (OTA) in 60 samples of green coffee beans from Brazil. The mycological evaluation was carried out using a conventional method and the OTA was determined using sequential phenyl silane and immunoaffinity column cleanup followed by HPLC. The detection limit was 0.2 microg kg(-1). Practically all samples (91.7%) were contaminated with moulds. The dominant fungal genus was Aspergillus, including A. niger (83.3%), A. ochraceus (53.3%) and A. flavus (25.0%). The occurrence and the levels of the genus Cladosporium (16.6%) and Penicillium (10.0%) were substantially lower than Aspergilli. Twenty samples (33.3%) of 60 were contaminated with the toxin at levels ranging from 0.2 to 7.3microg kg(-1). The average concentration was 2.38 microg kg(-1). All positive samples showed OTA levels below the limit suggested by the European Union (8 microg kg(-1)).

Brazil↗

Co-occurrence of patulin and citrinin in Portuguese apples with rotten spots.

Patulin and citrinin are mycotoxins produced by certain fungi mainly belonging to Penicillium and Aspergillus and may be detected in mouldy fruits and fruit products. The data presented here refer to the simultaneous occurrence of patulin and citrinin in 351 samples of seven different varieties of apples with small rotten areas (Casanova, Golden Delicious, Red Delicious, Reineta, Richared, Rome Beauty, Starking). A rapid multidetection thin layer chromatography (TLC) method was used. The minimum detectable concentrations of patulin and citrinin were 120-130 and 15-20 microg kg(-1) respectively. The percentage contamination with patulin only was higher (68.6%) than that with citrinin only (3.9%). Patulin and citrinin (19.6%) were also detected simultaneously. The highest mean patulin content was 80.50 mg kg(-1) for the Richared variety, but the mean level of citrinin was lower. The lowest mean contaminations of patulin were found in Rome Beauty, Red Delicious and Reineta, ranging from 3.06 to 5.37 mg kg(-1). All analysed apples varieties had low citrinin contamination, ranging from 0.32 to 0.92 mg kg(-1). These findings indicate that there may be a risk of human exposure to patulin through the consumption of juices and jams manufactured with apples with small rotten areas.

Chromatography, Thin Layer↗

Long-term biliary complications after liver surgery leading to liver transplantation.

Chronic biliary obstruction with repeated bouts of cholangitis adversely affects quality of life and may lead to secondary biliary cirrhosis with liver failure. We reviewed our experience with chronic biliary complications after surgical treatment of various diseases that at the end needed a liver transplantation. Twelve patients with previous biliary surgery developed secondary biliary cholangitis, secondary biliary cirrhosis, or both. Seven had surgery for liver hydatid disease by Echinococcus granulosus, another four had complicated biliary surgery unrelated to hydatid disease, and one had a history of a traffic accident with liver trauma and hepatectomy with chronic biliary fistula. The repeated cholangitis attacks and in two cases of hydatid disease the development of biliary-bronchial fistulas made these patients' lives miserable. All had had previous surgical procedures that made the transplantation procedure more difficult. Nevertheless, patient survival and graft actuarial survival after liver replacement were 75.0% and 69.2%, respectively, at 5 years.

Biliary Tract Diseases↗

[Glutaric aciduria type I: diagnosis in adulthood and phenotypic variability].

Glutaric aciduria typo I (GA I) is an uncommon metabolic disease with autosomal recessive inheritance. It usually presents in the first years of life and frequently causes movement disorders. Only a few cases have been diagnosed in adulthood. Two siblings who were diagnosed of GA I after a course of more than 20 years are reported here. The elder brother, after 9 months of normal psychomotor development, suffered from an acute encephalopathy with generalized hypotonia and, later on, dyskinetic movements. Throughout the following years severe generalized dystonia developed. The younger brother presented at 16 months with acute encephalopathy, hypotonia and generalized choreoathetoid movements. Cranial computed tomography showed in both patients an slight enlargement of Silvian cisures and diffuse white matter hypodensities. Magnetic resonance imaging performed in the second case disclosed in addition bilateral hyperintensities in putamen and caudate nucleous. At 29 and 24 years of age, respectively, an increased urinary excretion of glutaric and 3-hydroxiglutaric acids was detected in both patients. Glutaryl-CoA deshidrogenase activity in fibroblasts was absent in both. The patients were treated with carnitine and riboflavine, with no response. The present report shows that diagnosis of GA I should be considered in adults presenting a range of movement disorders from childhood.

Adolescent↗

Mechanism of free radical production in exhaustive exercise in humans and rats; role of xanthine oxidase and protection by allopurinol.

Exhaustive exercise generates free radicals. However, the source of this oxidative damage remains controversial. The aim of this paper was to study further the mechanism of exercise-induced production of free radicals. Testing the hypothesis that xanthine oxidase contributes to the production of free radicals during exercise, we found not only that exercise caused an increase in blood xanthine oxidase activity in rats but also that inhibiting xanthine oxidase with allopurinol prevented exercise-induced oxidation of glutathione in both rats and in humans. Furthermore, inhibiting xanthine oxidase prevented the increases in the plasma activity of cytosolic enzymes (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase) seen after exhaustive exercise. Our results provide evidence that xanthine oxidase is responsible for the free radical production and tissue damage during exhaustive exercise. These findings also suggest that mitochondria play a minor role as a source of free radicals during exhaustive physical exercise.

Adult↗

Age-related loss of proliferative activity of human vascular smooth muscle cells in culture.

This work studied the proliferation activity in cultures of vascular smooth muscle cells (SMC) from individuals of different ages. The cells derived from arteries of 12 donors of both sexes from 45 to 91 years of age. The main parameter considered was the 'proliferation rate' (cells grown per day in the different culture passages) taking into account the age of the donor. No significant relationship between age of the donor and the cell life in proliferation was found. On the contrary, the mean time of passage duration for reaching the maximum of proliferation as well as its 'efficiency' (maximum of proliferation rate registered/mean time of passage duration) show a statistically significant dependence on the age of the donor. Furthermore, the proliferation rate measured in each passage is statistically significant related to donor age. The regressions obtained show a similar negative slope (VC 4%). Considering the first five culture passages, the regression crosses the x-axis at the age of 105.6+/-11.7 years. This age in which no proliferative activity of human SMC would be expected lies near the limit of maximum life potential for human beings. Our results suggest that with advancing donor age there is an increasing number of senescent SMC either primarily transferred or appeared in the culture. Vascular SMC of individuals whose life is near the end would almost be all senescent and therefore show extremely low proliferation rates in the culture. If the proliferative activity of arterial SMC is a condition for atherogenesis, the proportion of senescent cells would be inversely related to the propensity of developing the atheroma because of the inability of these cells to divide.

Aged↗

Usefulness of pp65 antigenemia for the early diagnosis of cytomegalovirus disease in patients with AIDS.

An observational cohort study was performed to assess the effectiveness of a cytomegalovirus antigenemia (CMV-Ag) assay designed to predict clinical CMV disease in patients with AIDS. Eighty-six HIV-infected patients with CD4+ cell counts of < 100/mm3, positive CMV IgG, and no previous CMV disease were enrolled. Thirty-eight (44%) patients had at least one positive CMV antigenemia test, ten of whom eventually developed CMV focal disease. CMV disease was diagnosed in 13 (15%) patients. The CMV antigenemia assay was positive in ten of these 13 patients. Using a cut-off value of five positive cells in every 150,000 leukocytes sampled, the CMV antigenemia assay had a positive predictive value of 89% and a negative predictive value of 94%. The median time from the first positive CMV antigenemia test to the onset of CMV disease was 102 days. CMV disease probability at 6 months in patients with a CMV antigenemia value > or = 5 was 77.8% versus 6% in patients with CMV antigenemia value < 5 (log-rank test = 48.345; P < 0.001). Several independent factors were associated with the development of CMV disease: CMV antigenemia > or = 5 cells (hazard ratio: 20.44), CD4+ count < or = 25/mm3 (HR: 3.12), and sexual transmission of HIV infection (hazard ratio, 3.15). CMV antigenemia seems to be a good predictor of CMV disease in patients with AIDS.

AIDS-Related Opportunistic Infections↗

Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease.

In the present study, we hypothesized that exhaustive exercise in patients with chronic obstructive pulmonary disease (COPD) results in glutathione oxidation and lipid peroxidation and that xanthine oxidase (XO) contributes to free radical generation during exercise. COPD patients performed incremental cycle ergometry until exhaustion with (n = 8) or without (n = 8) prior treatment with allopurinol, an XO inhibitor. Reduced (GSH) and oxidized glutathione (GSSG) and lipid peroxides [malondialdehyde (MDA)] were measured in arterial blood. In nontreated COPD patients, maximal exercise (approximately 75 W) resulted in a significant increase in the GSSG-to-GSH ratio (4. 6 +/- 0.9% at rest vs. 9.3 +/- 1.7% after exercise). In nontreated patients, MDA increased from 0.68 +/- 0.08 nmol/ml at rest up to 1. 32 +/- 0.13 nmol/ml 60 min after cessation of exercise. In contrast, in patients treated with allopurinol, GSSG-to-GSH ratio did not increase in response to exercise (5.0 +/- 1.2% preexercise vs. 4.6 +/- 1.1% after exercise). Plasma lipid peroxide formation was also inhibited by allopurinol pretreatment (0.72 +/- 0.15 nmol/ml preexercise vs. 0.64 +/- 0.09 nmol/ml 60 min after exercise). We conclude that strenuous exercise in COPD patients results in blood glutathione oxidation and lipid peroxidation. This can be inhibited by treatment with allopurinol, indicating that XO is an important source for free radical generation during exercise in COPD.

Adenosine Triphosphate↗

Regulatory effects of cytokines and cyclosporine A on peripheral blood mononuclear cells from stable multiple sclerosis patients.

The proliferative response (PR) of peripheral blood mononuclear cells (PBMC) to lectins such as phytohemaglutinin (PHA), anti-CD3 monoclonal antibodies such as OKT-3 or phorbol esters such as tetradecanoyl-phorbol 13-acetate (TPA) was investigated in 18 stable multiple sclerosis (MS) patients (9 untreated and 9 treated patients) and 10 healthy controls. PBMC from untreated MS patients showed a significantly higher PR to PHA than healthy controls. The PR of PHA, anti-CD3 or TPA stimulated PBMC from treated patients was lower than that from untreated MS patients. Mitogen stimulated PBMC from untreated patients shown both increased sensitivity to the stimulatory effect of IL-2 and increased resistance to the inhibitory effect of IL-10 and IFN-alpha. The addition of IL-2 increased the PR in PHA-stimulated PBMC from untreated MS patients, but not in those from treated MS patients and healthy controls. Mitogen stimulated cells from untreated patients were more resistant to the inhibitory effect of IL-10 and IFN-alpha than PBMC from either treated MS patients or healthy controls. Cyclosporine A (CsA) inhibited the PR and the expression of activation antigens induced by PHA in PBMC from the three groups of subjects. This inhibitory effect of CsA have was enhanced by the addition of IFN-alpha.

Adult↗

[Paroxysmal dyskinesias as the initial manifestation of multiple sclerosis].

We herein report two patients with paroxysmal dyskinesias (PD) as the initial manifestation of multiple sclerosis (MS). PD can occur in clinically definite MS or rarely be the presenting symptom. They are produced by demyelinating lesions at any level in the motor pathway or in the thalamus. MRI disclosed an area of demyelination in the posterior limb of the internal capsule contralateral to the PD in the patients reported herein. PD associated with MS do not adjust completely to the accepted classifications of PD, therefore they should be considered a special category of dyskinesias.

Adult↗

[Retroperitoneal germinal tumor: extragonadal or burned out phenomenon of testicular primary? Presentation of a clinical case].

Clinical record case of a retroperitoneal seminoma with "burned-out" phenomenon in the testicular primary, in a 38 year old male with no background of interest who consults for a picture of left nephritic colic. The ipsilateral testis study detects a fibrotic area with hyalinosis and hemosiderin deposits, although there are no tumoral debris, compatible with the "burned-out" phenomenon. Management is through surgery plus a chemotherapy protocol. Discussion of the diagnostic algorithm of retroperitoneal tumours and the literature on extragonadal germinal tumours.

Adult↗