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Biomedical subjects

Y García

Publications and source records attributed to Y García.

18 recordsLinked to original sources

[Pharmacodynamic basis for the use of amoxicillin-clavulanic acid in respiratory infections due to Streptococcus pneumoniae: In vitro studies in an experimental model].

Amoxicillin-clavulanic acid is a first choice treatment for respiratory tract infections caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In a previous study we observed its high efficacy against penicillin-susceptible and intermediate-resistant strains of S. pneumoniae. We aimed to study the efficacy of this antibiotic against three strains of S. pneumoniae (susceptible, intermediate and resistant to penicillin) in a mouse model of pneumonia, and to determine the influence of the time of starting treatment and the in vitro postantibiotic effect. We also determined the serum levels of the antimicrobial agent in the mice, and correlated the pharmacodynamic parameters (Cmax/MIC, AUC/MIC and T>MIC) with the survival rate to establish the best predictor of efficacy. MICs with amoxicillin-clavulanic acid were 0. 03 mg/l, 0.25 mg/l and 2 mg/l for the penicillin-susceptible, -intermediate and -resistant strains, respectively. The ED90 were approximately 5 mg/kg for susceptible strains, 25 mg/kg for the intermediate and 50 mg/kg for the resistant strains. We observed a lower survival rate (approximately 55%) when the treatment began 31 h after infection than when it began 5 h (100%) and 19 h (approximately 90-100%) afterwards. Serum levels were dose dependent and the correlation with the pharmacodynamic parameters showed a significant association between survival and the T>MIC (r = 0.946). In vitro postantibiotic effects with 1, 4 and 10 times the MIC were 0.96 to 1.69 h for susceptible strains, 0.38 to 1.23 h for intermediate, and 1.52 to 2. 20 h for resistant strains. These results show the high efficacy of this antibiotic combination against strains with variable susceptibility to penicillin, with this activity being related mainly to the T>MIC of the microorganism. The postantibiotic effect would prolong the effect of the antibiotic in the dosing interval. These parameters and antimicrobial effects are important in terms of the clinical application of this antimicrobial agent.

Amoxicillin-Potassium Clavulanate Combination↗

Monitoring gamma-aminobutyric acid in human brain and plasma microdialysates using micellar electrokinetic chromatography and laser-induced fluorescence detection.

Due to its low electrophoretic mobility, few studies have been able to measure gamma aminobutyric acid (GABA) in biological samples by means of capillary zone electrophoresis. Nevertheless, in micellar electrokinetic chromatography (MEKC) by adding a surfactant to the mobile phase separation can be carried out on the basis of the partition coefficient of the molecules rather than their electrophoretic mobility. In the present study microdialysis coupled to MEKC with laser induced fluorescence detection was used to successfully monitor GABA from cerebrospinal fluid and plasma dialysates. Moreover, we monitored changes in extracellular GABA from a human brain. Microdialysis samples were collected from a Parkinson's disease patient undergoing a thallamotomy as part of her treatment. Significant decreases in extracellular GABA were detected during high frequency electrical stimulation and following a thermolesion of the thalamus. These results demonstrate the feasibility of MEKC coupled to laser-induced fluorescence detection in resolving neutral amino acids, specifically GABA, from different human body fluids.

Brain↗

Kinetics and mechanism of St I modification by peroxyl radicals.

St I is a toxin present in the Caribbean Sea anemone Stichodactyla helianthus which is highly hemolytic in the nanomolar concentration range. Exposure of the toxin to free radicals produced in the pyrolysis of 2,2'-azobis(2-amidinopropane) hydrochloride leads to a progressive loss of hemolytic activity. This loss of hemolytic activity is accompanied by extensive modification of tryptophan residues. On the average, three tryptophan residues are modified by each inactivated toxin. The loss of hemolytic activity of St I takes place without significant changes in the protein structure, as evidenced by the similarity of the fluorescence and CD spectra of native and modified proteins. Also, the native and modified ensembles present a similar resistance to their denaturation by guanidinium chloride. The hemolytic behavior and the performance of the toxin at the single-channel level when incorporated to black lipid membranes suggest that the modified ensemble can be considered as composed of inactive toxins and active toxins whose behavior is similar to that of the native proteins. These results, together with the lack of induction time in the activity loss, suggest that the fall of hemolytic activity takes place by an all-or-nothing inactivation mechanism in which the molecules become inactive when a critical amino acid residue is modified.

Amino Acids↗

Determinants of development of microalbuminuria in normotensive patients with type 1 and type 2 diabetes.

The purpose of this study was to identify the risk factors responsible for the development of microalbuminuria in diabetes. Two cohorts of 340 Type 1 and 258 Type 2 normotensive diabetic subjects were followed up for 24 months to evaluate progression to nephropathy. Sixteen Type 1 (4.7%) and 20 Type 2 (7.7%) patients developed persistent micro- or macroalbuminuria. Retinopathy, levels of glycated haemoglobin and the urinary albumin excretion rate (UAER) were indicative of progression in both cohorts. Cardiovascular disease in Type 1 and systolic blood pressure in Type 2 diabetes were the other risk factors. Logistic regression analysis showed that glycated haemoglobin levels [odds ratio (95% confidence interval) 2.08 (1.34, 3.21), p = 0.0007 in Type 1 and 1.77 (1.27, 2.45), p = 0.0005 in Type 2] and retinopathy [1.95 (1.09, 3.41), p = 0.02 in Type 1 and 2.87 (1.45, 5.69), p = 0.002 in Type 2] were risk factors in both cohorts. Male sex [2.06 (1.05, 4.03), p = 0.03] and the UAER [1.06 (1.001, 1.13), p = 0.04] in Type 1 patients, and systolic blood pressure [1.66 (1.05, 2.52), p = 0.02] in Type 2, were the other predictors. It is concluded that in normotensive Type 1 and Type 2 diabetic subjects glycemic control and retinopathy are the most important contributors to the development of incipient nephropathy.

Adult↗

[The postantibiotic effect of amoxicillin/clavulanic acid on Streptococcus pneumoniae strains of different serotypes and penicillin sensitivity].

Amoxicillin and clavulanic acid, combined in a 4:1 ratio, caused a significant (longer than 0.5 hours) postantibiotic effect (PAE) for the S. pneumoniae stains tested. These strains were from a different serotype (3, 6 and 9) and also had different susceptibility to penicillin. The duration of the PAE depended both on the strain and the amoxicillin/clavulanic acid concentration used. It is significant that for the serotype 9 strain, which was both penicillin and amoxicillin resistant, the duration of the PAE was between 1.5 and 2.2 hours. These results agree with those observed by other authors as to the effectiveness of amoxicillin/clavulanic acid against S.pneumoniae.

Amoxicillin-Potassium Clavulanate Combination↗

Activities against Streptococcus pneumoniae of amoxicillin and cefotaxime at physiological concentrations: in vitro pharmacodynamic simulation.

An in vitro model simulating amoxicillin and cefotaxime concentrations in human serum (after standard doses) was used to explore the activities of these drugs over time against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae strains. An initial inoculum reduction percentage of > or = 90% was obtained with amoxicillin and maintained for 2 to 8 h, regardless of the strain tested. In contrast, experiments showed that cefotaxime had significantly (P < 0.001) less capability to reduce initial inocula of the penicillin-resistant pneumococci from 0.5 h on than amoxicillin, despite the same in vitro susceptibility to amoxicillin and cefotaxime in both strains.

Amoxicillin↗

NMDA and non-NMDA receptor-mediated release of [3H]GABA from granule cell dendrites of rat olfactory bulb.

We have studied the effect of glutamate and the glutamatergic agonists N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on [3H]GABA release from the external plexiform layer of the olfactory bulb. The GABA uptake blocker nipecotic acid significantly increased the basal [3H]GABA release and the release evoked by a high K+ concentration, glutamate, and kainate. The glutamate uptake blocker pyrrolidine-2,4-dicarboxylate (2,4-PDC) inhibited by 50% the glutamate-induced [3H]GABA release with no change in the basal GABA release. The glutamatergic agonists NMDA, kainate, and AMPA also induced a significant [3H]GABA release. The presence of glycine and the absence of Mg2+ have no potentiating effect on NMDA-stimulated release; however, when the tissue was previously depolarized with a high K+ concentration, a significant increase in the NMDA response was observed that was potentiated by glycine and inhibited by the NMDA receptor antagonist 2-amino-5-phosphonoheptanoic acid (AP-7). The kainate and AMPA effects were antagonized by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not by AP-7. The glutamate effect was also inhibited by CNQX but not by the NMDA antagonist 2-amino-5-phosphonopentanoic acid (AP-5); nevertheless, in the presence of glycine, [3H]GABA release evoked by glutamate was potentiated, and this response was significantly antagonized by AP-5. Tetrodotoxin inhibited glutamate- and kainate-stimulated [3H]GABA release but not the NMDA-stimulated release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Incorporation of transferrin into the erythron in anemic and polycythemic conditions].

A ferrokinetic study was performed in 79 patients, 25 with absolute polycythaemia, 19 with relative polycythaemia and 35 presenting anaemia of different aetiology. The incorporation of transferrin into the erythron (ITE) was estimated on each case. The mean ITE values found in absolute primary and secondary polycythaemia and in secondary polycythaemia were, respectively, 281 +/- 85, 181 +/- 99 and 74 +/- 19 mumol/L tb/d (i.e., micromoles per litre of total blood per day). The mean ITE in iron deficiency anaemia was 110 +/- 43 mumol/L tb/d, in haemolytic anaemia this was 274 +/- 151 mumol/L tb/d, and in patients with myelodysplastic syndromes such values was 116 +/- 49 mumol/L tb/d. Significant differences were found for each group of patients with respect to a normal control group. Such findings are in accordance with the pathophysiology of the different pathologies studied. The values found in haemolytic anaemia and myelodysplastic syndromes are similar to those reported by others. The results of this study stress the advantages of evaluating the erythropoietic activity of the bone marrow by means of the ITE.

Adult↗

Use of ferrokinetics in the follow-up of patients with polycythaemia vera.

Periodical follow-up evaluations at intervals from 3 to 6 months of haematocrit, blood volume and ferrokinetic, during a 2.5 year period were performed in 18 polycythaemia vera (PV) patients to find the most characteristic parameters for the determination of the erythropoietic system functional activity. Our results suggest that in PV it is advisable to carry out further determination of red cell volume to determine exactly the degree of erythrocytosis. We found that plasma iron turnover (PIT) followed by 59Fe T1/2 are the first parameters to return to normal and the first to alter after a prolonged period of a normal ferrokinetic status. We suggest these may be used as the most reliable indicators for the haematological control of PV.

Aged↗

Circulating immune complexes in paroxysmal nocturnal hemoglobinuria.

Circulating immune complexes were investigated in sera of 13 patients with paroxysmal nocturnal hemoglobinuria. A significant inhibition was observed in the complement-dependent rosette formation (EAC) in 6 cases; 2 patients presented an increased anticomplementary activity; antilymphocyte antibodies were demonstrated in 2 patients. The levels of C3d and immunoconglutinins were also increased; there were no differences in the total hemolytic complement between patients and normal controls. There was a significant correlation between C3d and immunoconglutinins with the inhibition of the EAC rosette formation test. These results provide evidence for the presence of circulating immune complexes in paroxysmal nocturnal hemoglobinuria.

Adult↗

[The noninvasive study of cerebral veins and dural sinuses: comparison of two MR angiography techniques].

OBJECTIVE: To evaluate MR venography with bolus injection of intravenous contrast and elliptical filling of the K space, using three-dimensional fast spoiled gradient-echo (3D-FSPGR) sequences, and to compare it to the technique most frequently employed in the study of cerebral veins and dural sinuses, which is two-dimensional time-of-flight (2D-TOF) MR venography. MATERIAL AND METHODS: Source images, multiplanar reconstructions, and maximum intensity projections (MIP) were obtained using both 2D-TOF venography and contrasted-enhanced 3D-FSPGR venography in 20 healthy volunteers. Two radiologists independently evaluated both techniques for the visualization of twenty-one predefined venous structures, classifying the depiction as completely visible, partially visible, or not visible. RESULTS: The predefined venous structures were completely visible in 795 of 840 (94.6%) of the evaluations of contrast-enhanced 3D-FSPGR images versus 682 of 840 (81.1%) evaluations of 2D-TOF venography images. In the major dural sinuses, visualization was complete in 99.4% of the readings of contrast-enhanced 3D-FSPGR images versus 81% in the readings of the 2D-TOF images. CONCLUSION: 3D-FSPGR with elliptical filling of the K space and bolus injection of contrast material provides higher quality images of the intracranial venous system than those obtained using 2D-TOF sequences.

Adolescent↗

[Serum digoxin in children treated with beta methyl digoxin].

Concentrations of serum digoxin were measured by the polarized immunofluorescence Abbot TDx11 method in 59 samples from 53 children under treatment with mean beta methyl digoxin doses of 8.9 +/- 2.0 micrograms.kg.day. The therapeutic range for serum digoxin concentration was estimated to be 0.9 to 2.25 ng/ml. Simultaneous Na, K and creatine serum concentrations were measured. In 36 samples mean serum digoxin level was 1.52 +/- 0.45 ng/ml -within therapeutic range- and in only one of these cases clinical evidence of toxicity was apparent. In 15 samples digoxin level was above the therapeutic range and 11 patients of this group (73%) showed clinical signs of toxicity, consisting in arrythmias (six cases: supraventricular in 5 patients, ventricular in one child) and gastrointestinal symptoms (eight patients). Six patients with digoxin levels over therapeutic range and signs of digitalis toxicity had coincidental acute renal failure, which in 4 cases was subclinical--in 2 of these late it was pre-renal- and, in spite of this, all were inadvertently given the usual dosage of beta methyl digoxin. Almost invariably there was clinical evidence of toxicity when digoxin serum levels were above 2.4 ng/ml, so established maximal therapeutic level at 2.25 ng/ml seems adequate. Signs of digitalis toxicity must be looked on systematically in children treated with such drugs. In the critically ill or in children with acute renal failure it is necessary to monitor serum digoxin concentration. Among the clinical signs of toxicity, gastrointestinal symptoms are more frequent in children. An oral dose from 7 to 10 micrograms.kg.day of beta methyl digoxin in recommended.

Acute Kidney Injury↗