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Biomedical subjects

A Jiménez

Publications and source records attributed to A Jiménez.

At least 19 recordsLinked to original sources

Influence of the intensity, level and phase of spinal cord injury on the proliferation of T cells and T-cell-dependent antibody reactions in rats.

STUDY DESIGN: Three independent experiments in a rat model of contusive spinal cord (SC) injury were performed. Two studied the alterations induced by SC injury on some immunological aspects of the T-cell response. The third one evaluated the motor recovery of rats with low-thoracic injuries. OBJECTIVE: To examine the effect of level, intensity and phase of SC injury on T-cell proliferation and T-cell-dependent antibody response. SETTING: Neuroimmunology Department, UIMEN, IMSS-CAMINA Research Center. METHODS: Lymphocyte proliferation and hemagglutination assays were performed. Animals were injured either moderately or severely at T1 or T12 SC segments. Analysis of peripheral T-cell proliferation in response to mitogens and to myelin basic protein (MBP), as well as of antibody production against a T-dependent antigen, was performed at acute, subacute and chronic phases. RESULTS: A significant decrease of both response to mitogens and antibody production was found especially during the acute phase and in animals with severe and high (T1)-level injury. Animals with low (T12) and moderate contusions recovered to control levels at the chronic phase. An autoimmune reaction against MBP was observed only in animals with severe contusion at low level. CONCLUSIONS: The intensity, level and phase of SC injury differentially alter the function of T cells. These results will allow a better interpretation of studies directed to elucidate the role of T lymphocytes in various processes developed after SC injury.

Animals↗

Preservation of the liver graft with Celsior solution.

INTRODUCTION: We studied the evolution of the liver graft with preservation in Celsior (CS) compared with University of Wisconsin solution (UW). MATERIAL AND METHODS: A randomized prospective clinical study in 80 liver transplants (OLTs) from May 2001 to October 2003, compared CS (group I; n = 40) and UW (group II; n = 40). The characteristics of the donors were homogeneous, with no significant differences in 15 variables. CS was perfused with 4 L through the aorta, 2 L through the portal vein, and 1 L, through the portal vein on the back table; and the UW, as 3 L, 2 L, and 1 L, respectively. All OLTs were performed using the piggyback technique. RESULTS: Group I experienced reperfusion syndrome (n = 2; 5.9%), primary graft nonfunction (n = 0); vascular complications (n = 0); biliary anastomosis stenosis (n = 8; 22.9%), intensive care unit (ICU) days (n = 4.1 +/- 1), death within 30 days (n = 1; 3.1%). The patient and graft survivals at 1, 3, 6, 12, and 24 months were 93.7%, 93.7%, 90.2%, 85.7%, 85.7%, and 94.3%, 88.5%, 85.2%, 78%, 78%, respectively. For group II; the reperfusion syndrome occured in 6 patients (17.6%); primary graft nonfunction (n = 0); vascular complications (n = 0), biliary anastomosis stenosis (n = 3; 8.6%), ICU days (n = 4.9 +/- 2.4) and death within 30 days (n = 1; 3.1%); The patient and graft survival at 1, 3, 6, 12, and 24 months were 96.9%, 93.5%, 89.8%, 79.8%, 79.8% and 94.3%, 88.3%, 84.9%, 75.5%, 66.1%, respectively. CONCLUSIONS: CS offers the similar safety to UW for preservation of liver grafts within these ischemia times.

Adenosine↗

[Effects of nasal positive airway pressure treatment on oxidative stress in patients with sleep apnea-hypopnea syndrome].

OBJECTIVE: To analyze whether nasal continuous positive airway pressure (CPAP) reduces oxidative stress in patients with sleep apnea-hypopnea syndrome (SAHS). PATIENTS AND METHODS: Thirty-six patients with SAHS requiring nasal CPAP treatment and 10 controls in whom SAHS was ruled out were enrolled. Oxidative stress was evaluated by measuring plasma malondialdehyde (MDA) concentrations to assess lipid peroxidation at the beginning of the study and then again after a mean (SD) of 2.9 (0.6) months of nasal CPAP. Plasma MDA concentrations were determined by measuring thiobarbituric acid reactive substances. We controlled for the following factors known to influence oxidative stress: age, sex, use of vitamin supplements, smoking habit, body mass index (kg/m2), ischemic cardiopathy, hypertension, diabetes, and hypercholesterolemia. RESULTS: The mean age of patients with SAHS was 51.4 (9.9) years and the mean body mass index was 32.9 (5.3) kg/m2. Nasal CPAP was titrated to a mean pressure of 8.9 (3.4) cm H2O. The mean score on the Epworth sleepiness scale was 10.2 (4.3) before treatment and 4.2 (2.8) after treatment (P<.001). The apnea-hypopnea index decreased from 43.7 (22.6) before treatment to 4 (3.5) after treatment (P<.001). Mean MDA concentrations in patients with SAHS were 2.0 (1.1) micromol/mL before treatment and decreased significantly to 1.6 (.07) micromol/mL after treatment, whereas MDA concentrations remained unchanged in control subjects. CONCLUSIONS: Nasal CPAP treatment significantly reduced oxidative stress in patients with SAHS in our study.

Adult↗

Roles for redox regulation in leaf senescence of pea plants grown on different sources of nitrogen nutrition.

Leaf senescence and associated changes in redox components were monitored in commercial pea (Pisum sativum L. cv. Phoenix) plants grown under different nitrogen regimes for 12 weeks until both nodules and leaves had fully senesced. One group of plants was inoculated with Rhizobium leguminosarum and grown with nutrient solution without nitrogen. A second group was not inoculated and these were grown on complete nutrient solution containing nitrogen. Leaf senescence was evident at 11 weeks in both sets of plants as determined by decreases in leaf chlorophyll and protein. However, a marked decrease in photosynthesis was observed in nodulated plants at 9 weeks. Losses in the leaf ascorbate pool preceded leaf senescence, but leaf glutathione decreased only during the senescence phase. Large decreases in dehydroascorbate reductase and catalase activities were observed after 9 weeks, but the activities of other antioxidant enzymes remained high even at 11 weeks. The extent of lipid peroxidation, the number of protein carbonyl groups and the level of H(2)O(2) in the leaves of both nitrate-fed and nodulated plants were highest at the later stages of senescence. At 12 weeks, the leaves of nodulated plants had more protein carbonyl groups and greater lipid peroxidation than the nitrate-fed controls. These results demonstrate that the leaves of nodulated plants undergo an earlier inhibition of photosynthesis and suffer enhanced oxidation during the senescence phase than those from nitrate-fed plants.

Aging↗

Hypomethylation of DNA and resistance to apoptosis in tonsillar hypertrophy in children.

We analyzed the hypomethylation of DNA and the sensitivity to apoptosis of tonsillar cells and peripheral blood lymphocytes (PBL) in twenty children with either recurrent tonsillitis (RT) or tonsillar hypertrophy (TH). We found no significant differences in DNA methylation of PBL obtained from RT and TH groups. Hypomethylation of DNA extracted from tonsillar tissue was higher in TH than in RT and was associated with lower spontaneous and thapsigargin-induced apoptosis. By contrast, RT showed a low level of DNA hypomethylation and was associated with high sensitivity to spontaneous and thapsigargin-induced apoptosis.

Apoptosis↗

Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial.

BACKGROUND: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy. PATIENTS AND METHODS: A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m(2) administered every 3 weeks (3W arm) or docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity. RESULTS: One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis [1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032], while febrile neutropenia was significantly higher in the 3W arm [3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010]. CONCLUSIONS: Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.

Adult↗

Involvement of glutaredoxin-1 and thioredoxin-1 in beta-amyloid toxicity and Alzheimer's disease.

Strong evidence indicates oxidative stress in the pathogenesis of Alzheimer's disease (AD). Amyloid beta (Abeta) has been implicated in both oxidative stress mechanisms and in neuronal apoptosis. Glutaredoxin-1 (GRX1) and thioredoxin-1 (TRX1) are antioxidants that can inhibit apoptosis signal-regulating kinase (ASK1). We examined levels of GRX1 and TRX1 in AD brain as well as their effects on Abeta neurotoxicity. We show an increase in GRX1 and a decrease in neuronal TRX1 in AD brains. Using SH-SY5Y cells, we demonstrate that Abeta causes an oxidation of both GRX1 and TRX1, and nuclear export of Daxx, a protein downstream of ASK1. Abeta toxicity was inhibited by insulin-like growth factor-I (IGF-I) and by overexpressing GRX1 or TRX1. Thus, Abeta neurotoxicity might be mediated by oxidation of GRX1 or TRX1 and subsequent activation of the ASK1 cascade. Deregulation of GRX1 and TRX1 antioxidant systems could be important events in AD pathogenesis.

Adaptor Proteins, Signal Transducing↗

Diurnal variations in the plasma concentration of parathyroid hormone in dogs.

The plasma concentrations of parathyroid hormone (PTH), ionised calcium (Ca(2+)), total calcium, albumin and inorganic phosphorus, and the pH were measured in blood samples obtained from nine dogs during a period of 26 hours. The plasma pth levels fluctuated slightly during the day, by about 20 pg/ml, but there was a distinct peak (42.8 [8.8] pg/ml) at 07.00. Plasma Ca(2+) showed a diurnal pattern in which two peaks (increases of 0.03 mmol/l) were observed at 05.00 and 17.00, and the plasma concentration of inorganic phosphorus showed a similar pattern. There were no diurnal changes in total calcium or albumin.

Animals↗

Evidence in favour of a role for peripheral-type benzodiazepine receptor ligands in amplification of neuronal apoptosis.

The mitochondrial peripheral benzodiazepine receptor (PBR) is involved in a functional structure designated as the mitochondrial permeability transition (MPT) pore, which controls apoptosis. PBR expression in nervous system has been reported in glial and immune cells. We now show expression of both PBR mRNA and protein, and the appearance of binding of a synthetic ligand fluo-FGIN-1-27 in mitochondria of rat cerebellar granule cells (CGCs). Additionally, the effect of PBR ligands on colchicine-induced apoptosis was investigated. Colchicine-induced neurotoxicity in CGCs was measured at 24 h. We show that, in vitro, PBR ligands 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4- benzodiazepin-2-one (Ro5-4864) and diazepam (25- 50 microM) enhanced apoptosis induced by colchicine, as demonstrated by viability experiments, flow cytometry and nuclear chromatin condensation. Enhancement of colchicine-induced apoptosis was characterized by an increase in mitochondrial release of cytochrome c and AIF proteins and an enhanced activation of caspase-3, suggesting mitochondrion dependent mechanism that is involved in apoptotic process. Our results indicate that exposure of neural cells to PBR ligands generates an amplification of apoptotic process induced by colchicine and that the MPT pore may be involved in this process.

Animals↗

Mycobactericidal and tuberculocidal activity of Korsolex AF, an amine detergent/disinfectant product.

The mycobactericidal and tuberculocidal activities of Korsolex AF against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare (MAI), Mycobacterium kansasii and Mycobacterium chelonae were determined using quantitative suspension and carrier tests. The effects of organic load and hard water were also considered. A clinical isolate of MAI was the most resistant of the four test organisms. A 2% solution had good mycobactericidal and tuberculocidal activities after 30 min of exposure. Although further evaluation using European standard tests is necessary, we conclude that Korsolex AF appears to be a promising product for the disinfection of hospital instruments contaminated with mycobacteria.

Amines↗

Flavopiridol: an antitumor drug with potential application in the treatment of neurodegenerative diseases.

Several lines of evidence show that cyclin-dependent kinases (CDKs) contribute to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, and amyotrophic lateral sclerosis. Given their role in the neuronal apoptosis, the inhibition of CDKs by specific drugs such as flavopiridol may be a valid therapeutic approach. Expression of CDKs was observed in rodent models of excitotoxicity and stroke, and CDK inhibitors showed neuroprotective effects. Flavopiridol may provide significant improvement in neurodegenerative diseases in humans.

Animals↗

Implication of cyclin-dependent kinase 5 in the neuroprotective properties of lithium.

Although numerous studies have demonstrated a neuroprotective and anti-apoptotic role of lithium in neuronal cell cultures, the precise mechanism by which this occurs, remains to be elucidated. In this study, we evaluated the lithium-mediated neuroprotection against colchicine-induced apoptosis in cultured cerebellar granule neurons. Previously, it has been demonstrated that colchicine mediates apoptosis in cerebellar granule neurons through cytoskeletal alteration and activation of an intrinsic pro-apoptotic pathway. Recently we also demonstrated a potential role of cyclin-dependent kinase 5 (cdk5) in this pathway. Here we report that colchicine induces dephosphorylation in Ser-9 and phosphorylation in Tyr-216, and thus activation, of glycogen synthase kinase-3beta in cerebellar granule neurons, and that this modification is inhibited by the presence of 5 mM lithium. However, the selective glycogen synthase kinase-3beta inhibitors SB-415286 and SB-216763 were unable to prevent colchicine-induced apoptosis in these cells, suggesting that the anti-apoptotic activity of lithium is not mediated by glycogen synthase kinase-3beta under these conditions. On the other hand, 5 mM lithium prevented the colchicine-induced increase in cdk5 expression and breakdown of cdk5/p35 to cdk5/p25. In addition, we show that up-regulation of cdk5/p25 is unrelated to inhibition of the activity of myocyte enhancer factor 2, a pro-survival transcription factor. These data suggest a previously undescribed neuroprotective mechanism of lithium associated with the modulation of cdk5/p35 or cdk5/p25 expression.

Aminophenols↗

Severe hepatotoxicity due to anti-tuberculosis drugs in Spain.

OBJECTIVES: To determine the frequency of severe hepatotoxicity due to anti-tuberculosis (TB) drugs, and predictors of development of acute liver failure or of death. METHODS: A retrospective study conducted by members of the Spanish Society of Pneumology from 18 hospitals during 1997-2001. A case of severe hepatotoxicity was defined as any asymptomatic patient with a ten-fold increase in transaminases or three-fold increase in colostasis parameters, or, among patients with hepatitis symptoms, any raised hepatic parameters or development of hepatic failure. Predictive factors were studied using logistic regression, calculating odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: One hundred and six patients developed severe hepatotoxicity. Of a total of 3510 patients, 90 were treated for active TB (2.56%). Eleven cases (10.3%) presented with acute liver failure, three of whom underwent liver transplant. The global case fatality rate was 4.7% (five cases, three associated with alcohol use or hepatotoxic drugs). The predictors of poor prognosis were total bilirubin > 2 mg/dl (OR 9.4, 95% CI 1.0-85.5) and serum creatinine > 1.5 mg/dl (OR 32.1, 95% CI 2.4-424.6). CONCLUSIONS: Severe hepatotoxicity due to anti-tuberculosis drugs is associated with a high fatality rate. Prevention should be based on informing patients and frequent clinical and laboratory controls.

Adult↗

Application of solid-phase microextraction to the analysis of volatile compounds in virgin olive oils.

Solid-phase microextraction was used as a technique for headspace sampling of extra virgin olive oil and virgin olive oil samples with different off-flavours. A 100 microm coated polydimethylsiloxane fiber was used to extract volatile aldehydes, the sampling temperature was 45 degrees C and the fiber has been exposed to the headspace for 15 min. Nonanal and 2-decenal were present in all the olive oils with extraction off-flavours but were not in extra virgin olive oil sample.

Aldehydes↗

Characterization and hardening of concrete with ultrasonic testing.

In this study, we describe a technique which can be used to characterize some relevant properties of 26 cylindrical samples (15 x 30 cm2) of concrete. The characterization has been performed, according to Spanish regulations in force, by some destructive and ultrasound-based techniques using frequencies of 40 kHz. Samples were manufactured using different water/cement ratios (w/c), ranging from 0.48 to 0.80, in order to simulate different values of compressive strength at each sample. We have correlated the propagation velocity v of ultrasonic waves through the samples to compressive strength R values. As some other authors remark, there exists an exponential relationship between the two above parameters. We have found that a highly linear relationship is present between R and w/c concentration at the samples. Nevertheless, when the same linear model is adopted to describe the relationship between v and w/c, the value of r decreases significantly. Thus, we have performed a multiple regression analysis which takes into account the impact of different concrete constituents (water, cement, sand, etc.) on ultrasound propagation speed. One of the most relevant practical issues addressed in our study is the estimation of the hardening curve of concrete, which can be used to quantify the viability of applying the proposed method in a real scenario. Subsequently, we also show a detailed analysis of the temporal evolution of v and R through 61 days, beginning at the date where the samples were manufactured. After analyzing both parameters separately, a double reciprocal relationship is deduced. Using the above parameters, we develop an NDE-based model which can be used to estimate hardening time of concrete samples.

Journal Article↗