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Biomedical subjects

C Díaz

Publications and source records attributed to C Díaz.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Aplasia after azathioprine administration: role of the thiopurine methyltransferase genetic polymorphism].

BACKGROUND: Azathioprine is an immunosuppressor drug widely used in the treatment of autoimmune diseases. Adverse effects during treatment are related to the activity of thiopurine methyltransferase (TPMT), an enzyme which plays a role in azathioprine metabolism. The presence of the allelic variants of the TPMT gene allows us to classify patients into three different groups: high, moderate and low risk of myelosuppression after receiving standard doses of azathioprine. PATIENTS AND METHODS: Study of the allelic variants of the TPMT gene in the positions 460 and 719 with PCR methods in a patient with Crohn's disease, who developed aplasia after receiving azathioprine. The study was extended to his relatives. RESULTS: The patient under study carried the most frequent variant allele of the TPMT gene associated with low enzymatic activity. The mother and one sister of the patient were also carriers of this allelic variant. CONCLUSIONS: Genotyping the allelic variants of the TPMT gene is a useful method to identify patients at moderate or high risk of myelosuppression after administration of azathioprine.

Adult↗
PubMed2000

Effects of medium on decarboxylation kinetics: 3-carboxybenzisoxazoles and their potential use as environmental probes in biochemistry.

The decarboxylation rate of the tetramethylguanidinium salt of 3-carboxy-6-nitrobenzisoxazole in 24 pure solvents and 36 dimethyl sulfoxide binary mixtures with diglyme, acetonitrile, benzene, dichloromethane, chloroform, and methanol was analyzed in the light of the SPP, SA, and SB pure solvent scales. The results allow one to rationalize the high sensitivity of this kinetics to the reaction medium and to assess the potential use of this compound as a probe in biochemical environments. The natural environment for comparison of this kinetics was found to be the gas phase rather than the aqueous medium. In the latter, the process is much faster owing to such high polarity, which, however, is strongly diminished by the high acidity of the medium. Based on our calculations, the rate constant for the decarboxylation kinetics in the gas phase must be in the region of 2 x 10(-10) s(-1) (i.e., 3 orders of magnitude smaller than in water).

Decarboxylation↗
PubMed2000

Aging and the human vestibular nuclei: morphometric analysis.

The data concerning the effects of age on the brainstem are scarce and few works are devoted to the human vestibular nuclear complex. The study of the effects of aging in the vestibular nuclei could have clinical interest due to the high prevalence of balance control and gait problems in the elderly. We have used in this work eight human brainstems of different ages sectioned and stained by the formaldehyde-thionin technique. The neuron's profiles were drawn with a camera lucida and Abercrombie's method was used to estimate the total number of neurons. The test of Kolmogorov-Smirnov with the correction of Lilliefors was used to evaluate the fit of our data to a normal distribution and a regression analysis was done to determine if the variation of our data with age was statistically significant. Aging does not affect the volume or length of the vestibular nuclear complex. Our results clearly show that neuronal loss occurs with aging in the descending (DVN), medial (MVN), and lateral (LVN) vestibular nuclei, but not in the superior (SVN). There are changes in the proportions of neurons of different sizes but they are not statistically significant. The neuronal loss could be related with the problems that elderly people have to compensate unilateral vestibular lesions and the alterations of the vestibulospinal reflexes. The preservation of SVN neurons can explain why vestibulo-ocular reflexes are compensated after unilateral vestibular injuries.

Adult↗
PubMed2000

The protective role of atorvastatin on function, structure and ultrastructure in the aorta of dyslipidemic rabbits.

Responses to both an endothelium-dependent (acetylcholine 10(-9)-10(-5) mol/l) and an endothelium-independent vasodilator (sodium nitroprusside 10(-10)-10(-6) mol/l) were studied in aortic rings from rabbits fed or not with a diet containing 0.5% cholesterol plus 14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg/kg/day). Morphometric and ultrastructure analyses were also performed. Rabbits fed the dyslipidemic diet presented higher plasma cholesterol and triglyceride concentrations than controls (P < 0.05). This was associated with intima-media thickening and, consequently, aortic stenosis (29 +/- 3%) since vessel cross-sectional area did not change. Endothelial cells presented numerous alterations in dyslipidemic rabbits. Atorvastatin treatment only reduced plasma levels in dyslipidemic rabbits (P < 0.05), which were nevertheless higher than those of controls. In addition, it prevented the reduction in acetylcholine relaxation in hypercholesterolemic animals. Atorvastatin administration also enhanced the response to acetylcholine in rabbits fed a control diet. Likewise, atorvastatin treatment reduced lesion area and consequently increased aortic lumen in dyslipidemic rabbits but did not modify media thickening. It also prevented the majority of the ultrastructural changes observed in endothelial cells. In conclusion, chronic atorvastatin treatment exerts a protective role in vascular function, structure and ultrastructure even in the presence of high cholesterol and triglyceride plasma levels.

Animals↗
PubMed2000

Short- and long-term effects of atorvastatin, lovastatin and simvastatin on the cellular metabolism of cholesteryl esters and VLDL secretion in rat hepatocytes.

The short- and long-term in vitro effects of the hydroxymethylglutaryl-CoA reductase inhibitor atorvastatin, compared with lovastatin and simvastatin on VLDL secretion, and on the formation and the neutral and acid lysosomal hydrolysis of cholesteryl esters was investigated in rat liver hepatocytes maintained in suspension (2 or 4 h) or cultured in monolayers (24 h). All statins time-dependently reduced [14C]oleate incorporation into cholesteryl esters, but when exogenous cholesterol was added only atorvastatin caused an immediate transient decrease in hepatocyte ACAT activity. Activity of the lysosomal, microsomal and cytosolic CEH isoforms was unaffected by the hepatocyte treatments. Statins reduced free and esterified cholesterol mass in hepatocyte microsomes after 2 h, and this was followed by a modest decline in VLDL cholesteryl esters, whilst secretion of VLDL apoB and triglycerides was unaltered. However, after 24 h of treatment, statins caused generalized 20-40% decreases in the secretion of VLDL apoB, cholesterol and triglycerides, with the reduction in apoB48 secretion being significantly superior to that caused in apoB100. The mean diameter of secreted VLDL was not modified by either duration or drug treatment. Additional studies with subcellular fractions demonstrated that statins have a direct selective effect on the enzymes governing the cholesterol-cholesteryl ester cycle, with the exception of the microsomal CEH. Atorvastatin, lovastatin and simvastatin inhibited ACAT activity in microsomes by 50% at doses of 250, 100 and 50 microM, respectively. The cytosolic CEH elicited a biphasic profile of activity with activations up to 100 microM statin and inhibitions above 250 microM, and the lysosomal CEH was only inhibited by atorvastatin at a dose of 100 microM or more. We conclude that a prolonged, but not a short, limited availability of hepatocyte cholesterol derived from the endogenous synthesis reduces VLDL secretion, and that reactivity of statins at the cellular level are more similar than reactivity at the subcellular level as regards the cholesterol-cholesteryl ester cycle.

Animals↗
PubMed2000

Myotoxic phospholipases A(2) in bothrops snake venoms: effect of chemical modifications on the enzymatic and pharmacological properties of bothropstoxins from Bothrops jararacussu.

Venoms from eight Bothrops spp. were fractionated by ion-exchange chromatography on CM-Sepharose at pH 8.0 for the purification of myotoxins. Chromatographic profiles showed differences regarding myotoxic components among these venoms. B. alternatus, B. atrox and B. jararaca venoms did not show the major basic myotoxic fractions identified in the other venoms. Polyacrylamide gel electrophoresis for basic proteins also showed distinct patterns for these toxins. In vivo, all the isolated myotoxins induced release of creatine kinase due to necrosis of muscle fibers, accompanied by polymorphonuclear cell infiltration, and edema in the mouse paw. In addition, the toxins showed cytotoxic and liposome-disrupting activities in vitro. B. jararacussu bothropstoxins-I (BthTX-I) and II (BthTX-II) were submitted to chemical modifications of: His, by 4-bromophenacyl bromide (BPB) or photooxidation by Rose Bengal (RB); Tyr, by 2-nitrobenzenesulphonyl fluoride (NBSF); and Trp, by o-nitrophenylsulphenyl chloride (NPSC). The myotoxic and cytotoxic activities of BthTX-I, a Lys49 PLA(2) homologue, after modification by BPB, RB, NBSF and NPSC, were reduced to 50%, 20%, 75%, 65% and 13%, 0.5%, 76%, 58%, respectively. However, the edema-inducing and liposome-disrupting activities were not significantly reduced by the above modifications. BPB-treated BthTX-II, an Asp49 PLA(2) homologue, lost most of its catalytic, indirect hemolytic, anticoagulant, myotoxic and cytotoxic activities. The edema-inducing and liposome-disrupting activities were reduced to 50% and 80%, respectively. Lethality caused by BthTX-I and -II was strongly reduced after treatment with BPB or RB, but only partially with NBSF or NPSC. BthTX-I and -II, both native or modified, migrated similarly in a charge-shift electrophoresis. Antibodies raised against BthTX-I or -II, B. asper Basp-II and the C-terminal 115-129 peptide from Basp-II did not show significant differences in their cross-reactivity with the modified toxins, except with RB photooxidized toxins.

Animals↗
PubMed2000

Cytoarchitectonic subdivisions in the subtectal midbrain of the lizard Gallotia galloti.

Contemporary study of molecular patterning in the vertebrate midbrain is handicapped by the lack of a complete topological map of the diverse neuronal complexes differentiated in this domain. The relatively less deformed reptilian midbrain was chosen for resolving this fundamental issue in a way that can be extrapolated to other tetrapods. The organization of midbrain centers was mapped topologically in terms of longitudinal columns and cellular strata on transverse, Nissl-stained sections in the lizard Gallotia galloti. Four columns extend along the whole length of the midbrain. In dorsoventral order: 1) the dorsal band contains the optic tectum, surrounded by three ventricularly prominent subdivisions, named griseum tectale, intermediate area and torus semicircularis, in rostrocaudal order; 2) a subjacent region is named here the lateral band, which forms the ventral margin of the alar plate and also shows three rostrocaudal divisions; 3) the basal band forms the basal plate or tegmentum proper; it appears subdivided into medial and lateral parts: the medial part contains the oculomotor and accessory efferent neurons and the medial basal part of the reticular formation, which includes the red nucleus rostrally; the lateral part contains the lateral basal reticular formation, and includes the substantia nigra caudally; 4) the median band contains the ventral tegmental area, representing the mesencephalic floor plate. The alar regions (dorsal and lateral) show an overall cellular stratification into periventricular, central and superficial strata, with characteristic cytoarchitecture for each part. The lateral band contains two well developed superficial nuclei, one of which is commonly misidentified as an isthmic formation. The basal longitudinal subdivisions are simpler and basically consist of periventricular and central strata.

Animals↗
PubMed2000

Simultaneous presence of C-ANCA and P-ANCA in a patient with concurrent Churg-Strauss syndrome and giant cell temporal arteritis.

We herein describe the case of a 77-year-old woman, who presented clinical and histopathological evidence of giant cell arteritis (GCA) involving the temporal artery, together with a Churg-Strauss syndrome (CSS). Our patient presented positive anti-neutrophil cytoplasmic antibodies (ANCA), with cytoplasmic staining pattern (C-ANCA) that was specific against proteinase 3 (PR3), and also a perinuclear pattern (P-ANCA) with specificity against myeloperoxidase (MPO). To our knowledge, the simultaneous presence in the same patient of both types of antibodies has not been previously reported.

Aged↗
PubMed2000

Systemic hemodynamics, gastric intramucosal PCO2 changes, and outcome in critically ill burn patients.

OBJECTIVES: To define the hemodynamic and gastric intramucosal PCO2 (PiCO2) changes during the first 48 hrs after burn trauma and to analyze their relationship with outcome. DESIGN: Prospective, observational study in a cohort of consecutively admitted critically ill burn patients. SETTING: Intensive care burn unit in a university hospital. PATIENTS: Forty-two patients with burns covering >20% of body surface area or inhalation injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were monitored with an oximetric pulmonary arterial catheter and a gastric tonometer to measure PiCO2. The difference between arterial and gastric mucosal PCO2 (P[i-a]CO2) was considered indicative of gastric mucosal hypoxia. Hemodynamic and PiCO2 measurements were performed during the first 48 hrs after admission. Patients suffered burns covering 36.1% +/- 14.3% (mean +/- SD) and 45.3% +/- 21.9% of body surface area (survivors and nonsurvivors, respectively). All patients were successfully resuscitated by conventional standards. Nonsurvivors (n = 16) died a median of 17 days after admission. In univariate analysis, the presence of shock during the resuscitation phase, age, mixed venous pH, P[i-a]CO2, right atrial pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac index, systemic and pulmonary vascular resistance, left ventricular stroke work index, mixed venous oxygen saturation, and systemic oxygen delivery, consumption, and extraction ratio, measured over the first 12 hrs after admission, were significantly (p < .05) different between survivors and nonsurvivors. These differences disappeared after 12 hrs after admission. Multivariate analysis identified age, percentage body surface area burned, and oxygen delivery index (6 hrs after admission) as factors independently associated with a poor outcome. P[i-a]CO2 (12 hrs after admission) was significantly greater in patients with than in those without inhalation injury (17 +/- 13 torr [2.26 +/- 1.73 kPa] vs. 6 +/- 10 torr [0.79 +/- 1.33 kPa]; p = .005). Patients with a P[i-a]CO2 difference (6 hrs after admission) > or =10 torr (1.33 kPa) had a mortality rate of 56% vs. 25% of those patients with <10 torr (p = .044). CONCLUSIONS: Our data indicate that there are hemodynamic and biochemical changes that occur early after burn trauma that are associated with prognosis after an apparently successful resuscitation. Particularly, a hemodynamic profile characterized by systemic acidosis, low systemic blood flow, and systemic and pulmonary vasoconstriction early after trauma is associated with a poor outcome. Additionally, intestinal mucosal acidosis occurs after burn trauma, is influenced by inhalation injury, and is a variable related to outcome.

Adolescent↗
PubMed2000

Protective effects of zinc on cadmium toxicity in rodents.

A study of acute and subacute toxicity of cadmium ions [Cd(II)] was carried out on male Swiss mice and Sprague-Dawley rats with and without previous administration of zinc chloride. The LD50 of Cd(II) as cadmium sulfate (ip) was lower in animals previously given 10 mg/kg of zinc(II) chloride (sc). Factors such as animal weight variations, biochemical parameters, and accumulation patterns of Cd(II) and Zn(II) were taken into consideration when the subacute toxicity was evaluated. Alteration of the activities of glutamic pyruvic transaminase (GPT) and of glutamic oxaloacetic transaminase (GOT) was observed in short-term-exposure (<6 h) cases. These alterations reverted to normal after 1 wk. The activity of alkaline phosphatase (ALP) and the concentrations of cholesterol and triglycerides in serum are also changed, especially so in the groups given CdSO4 alone. In the experimental groups treated with ZnCl2 prior to administration of cadmium, proteinuria was detected 5 wk after the treatment. Also at 5 wk, both Zn-treated and nontreated groups showed an abnormally low liver mass with respect to total body mass. Both Cd and Zn are retained preferentially in the liver but show also in the kidneys. If CdSO4 and ZnCl2 are given simultaneously, especially after 1 wk of treatment, Cd is accumulated in greater amounts in these organs when compared to the groups given only cadmium sulfate.

Animals↗
PubMed2000

[Prospective assessment of clinical outcomes in patients with lung cancer].

BACKGROUND: The aim of this study was to assess the outcome in patients with lung cancer. PATIENTS AND METHODS: Prospective study in 93 patients with lung cancer in 3 community hospitals. In each evaluation (4-6 weeks) the following results were obtained: a) questionnaire on the quality of life or performance status (QoL/PS), based on different instruments (Karnofsky Performance Scale [KPS], ECOG, QLQ-C30, and the Nottingham Health Profile [NHP], and b) a clinical questionnaire. Active follow-up was for 18 months and survival tracking was to five years. A descriptive analysis of the outcome variables and a survival analysis (Kaplan-Meier) were done. The prognostic value of each instrument (Cox) and the correlation between the instruments (Spearman) were also evaluated. RESULTS: The mean values recorded at the time of diagnosis between 60% and 70% of the maximum value possible. Mean survival was 12.4 months; accumulated survival was 30% to one year and 4% to 55 months. Only 17% of patients presented any disease-free period. Toxicity of treatment was almost always irrelevant. The correlation between the KPS, the QLQ-30 and the NHP was acceptable and their initial values were important prognostic factors. The QoL/PS scores for the survivors were similar to their initial values, but the global values were 11%. CONCLUSIONS: The outcomes measures used in this study provide very useful information, although registration and analysis of the necessary data should be systematic. The KPS was comparable to the other QoL/PS indicators used, but it is shorter, more acceptable and easier to use. Better QoL/PS measurement instruments are needed to evaluate outcomes in the practice of clinical oncology.

Adult↗
PubMed1999

Crystal structure of myotoxin II, a monomeric Lys49-phospholipase A2 homologue isolated from the venom of Cerrophidion (Bothrops) godmani.

Lys49-Phospholipase A2 (Lys49-PLA2) homologues damage membranes by a Ca2+-independent mechanism which does not involve catalytic activity. With the aim of determining the structural basis for this novel activity, we have solved the crystal structure of myotoxin-II, a Lys49-PLA2 isolated from the venom of Cerrophidion (Bothrops) godmani (godMT-II) at 2.8 A resolution by molecular replacement. The final model has been refined to a final crystallografic residual (Rfactor) of 18.8% (Rfree = 28.2%), with excellent stereochemistry. godMT-II is also monomeric in the crystalline state, and small-angle X-ray scattering results demonstrate that the protein is monomeric in solution under fisicochemical conditions similar to those used in the crystallographic studies.

Animals↗
PubMed1999

Atorvastatin reduces NF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells.

Cardiovascular mortality, mainly due to the rupture of unstable atherosclerotic plaques, is reduced by 3-hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Inflammatory cells, attracted to the vascular lesion by chemokines, have been implicated in the process of the plaque rupture. In cultured vascular smooth muscle cells (VSMC) and U937 mononuclear cells we have studied the effect of Atorvastatin (Atv) on nuclear factor kappaB (NF-kappaB) activity, an inducer of the mRNA expression of chemokines such as interferon-inducible protein 10 (IP-10) and monocyte chemoattractant protein 1 (MCP-1). Angiotensin II (Ang II) and tumor necrosis factor alpha (TNF-alpha) increased NF-kappaB activity in VSMC (2 and 5-fold, respectively). Preincubation of cells with 10(-7) mol/l Atv diminished this activation (44 and 53%). The inhibition was reversed by mevalonate, farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP), but not by other isoprenoids. Coinciding with the NF-kappaB activation in VSMC, there was a diminution of cytoplasmic IkappaB levels that was recovered by pretreatment with Atv. Ang II and TNF-alpha induced the expression of IP-10 (1.5 and 3.4-fold) and MCP-1 (2.4 and 4-fold) in VSMC. Atv reduced this overexpression around 38 and 35% (IP-10), and 54 and 39% (MCP-1), respectively. Our results strongly suggest that Atv, through the inhibition of NF-kappaB activity and chemokine gene expression, could reduce the inflammation within the atherosclerotic lesion and play a role in the stabilization of the lesion.

Animals↗
PubMed1999

Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits.

The effects of atorvastatin (3 mg kg(-1)) and simvastatin (3 mg kg(-1)) on hepatic enzyme activities involved in very low density lipoprotein metabolism were studied in coconut oil/cholesterol fed rabbits. Plasma cholesterol and triglyceride levels increased 19 and 4 fold, respectively, after 7 weeks of feeding. Treatment with statins during the last 4 weeks of feeding abolished the progression of hypercholesterolaemia and reduced plasma triglyceride levels. 3-Hydroxy-3-methyl-glutaryl Coenzyme A reductase, acylcoenzyme A:cholesterol acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities were not affected by drug treatment. Accordingly, hepatic free cholesterol, cholesteryl ester and triglyceride content were not modified. Simvastatin treatment caused an increase (72%) in lipoprotein lipase activity without affecting hepatic lipase activity. Atorvastatin caused a reduction in hepatic phospholipid content and a compensatory increase in CTP:phosphocholine cytidylyl transferase activity. The results presented in this study suggest that, besides the inhibitory effect on 3-hydroxy-3-methyl-glutaryl Coenzyme A reductase, simvastatin and atorvastatin may have additional effects that contribute to their triglyceride-lowering ability.

Acyl Coenzyme A↗
PubMed1999

Diencephalic neuronal populations projecting axons into the basal plate in a lizard (Gallotia galloti).

Lizard diencephalic populations sending axons into the basal plate were studied by the in vitro HRP technique in the lizard Gallotia. Retrograde labeled cells were concentrated in distinct neuronal groups within alar plates of prosomeres p1 and p3, whereas the alar plate of p2 was poorly labeled. Efferent fibers from alar p1 and p3 populations entered the basal plate of the diencephalon along topologically dorsoventral courses, bifurcating thereafter into longitudinal ascending (rostral) and descending (caudal) trajectories. Thus, diencephalic segments p1 and p3 have alar cell populations contributing to the longitudinal premotor connectivity of the neural axis , whereas the alar p2 segment projects via the fasciculus retroflexus, the efferent tract of the epithalamus. However, the axons from the habenular complex bifurcate within or adjacent to the floor plate and not within the basal plate.

Animals↗