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Biomedical subjects

J Barra

Publications and source records attributed to J Barra.

At least 37 records · Page 2Linked to original sources
PubMed1998

Can the organization of a binary mix be predicted from the surface energy, cohesion parameter and particle size of its components?

PURPOSE: The aim of this study was to relate the organization of several binary mixes with three physical parameters (surface energy, cohesion parameter, and particle size) of various materials blended with each other. METHODS: Four pharmaceutical compounds were selected for their surface energies and cohesion parameters. Binary mixes were prepared from different sieved fractions. The frequency and nature of the interactions between the particles were observed by scanning electron microscopy. RESULTS: As expected, interactions were determined by both the energetics and the relative particle size of the two compounds blended, the latter determining the mode of interaction. However, particle size was not the only factor influencing the organization of the blends as, sometimes, small particles of a material would not adhere to the coarser particles of the other. Thus, a surface energy derived parameter ¿(B/A)lambda - (A/B)lambda¿ appears to be a valuable estimating tool of the potentiality of interaction between the particles blended. No correlation between the cohesion parameters of the compounds and the organization of the resulting blends could be found. CONCLUSIONS: Surface energy and particle size play a major role in the organization of a binary blend. However, they cannot explain separately the interactions observed between the fractions blended as reliable predictions require the use of both characteristics.

Adhesiveness↗
PubMed1998

Partial-solubility parameters of naproxen and sodium diclofenac.

The expanded Hansen method was tested for determination of the solubility parameters of two non-steroidal anti-inflammatory drugs, naproxen and sodium diclofenac. This work describes for the first time the application of the method to the sodium salt of a drug. The original dependent variable of the expanded Hansen method, involving the activity coefficient of the drug, was compared with the direct use of the logarithm of the mole fraction solubility 1nX2 in the solubility models. The solubility of both drugs was measured in pure solvents of several chemical classes and the activity coefficient was obtained from the molar heat and the temperature of fusion. Differential scanning calorimetry was performed on the original powder and on the solid phase after equilibration with the pure solvents, enabling detection of possible changes of the thermal properties of the solid phase that might change the value of the activity coefficient. The molar heat and temperature of fusion of sodium diclofenac could not be determined because this drug decomposed near the fusion temperature. The best results for both drugs were obtained with the dependent variable 1nX2 in association with the four-parameter model which includes the acidic and basic partial-solubility parameters delta(a) and delta(b) instead of the Hansen hydrogen bonding parameter delta(h). Because the dispersion parameter does not vary greatly from one drug to another, the variation of solubility among solvents is largely a result of the dipolar and hydrogen-bonding parameters, a fact that is being consistently found for other drugs of small molecular weight. These results support earlier findings with citric acid and paracetamol that the expanded Hansen approach is suitable for determining partial-solubility parameters. The modification introduced in the expanded Hansen method, i.e. the use of 1nX2 as the dependent variable, provides better results than the activity coefficient used in the original method. This is advantageous for drugs such as sodium diclofenac for which the ideal solubility cannot be estimated. This paper shows for the first time that the method is suitable for determination of the partial-solubility parameters of a sodium salt of a drug, sodium diclofenac.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

[Vascular dysfunction in hypertension evaluated by nonivasive assessment of arterial impedance].

The effects of high blood pressure on arterial vessels has become an important topic of research. These effects can be evaluated by analyzing three major components: systemic vascular resistance, arterial compliance and wave reflection. The increase in systemic vascular resistance and arterial stiffness produces modifications of left ventricular afterload and morphologic changes of pressure and flow waves. These effects can eventually cause structural changes of the left ventricle, an increase in oxygen consumption and a decrease in coronary perfusion. Until recently, invasive methods were the only means to evaluate arterial function. The aim of this review is to assess the usefulness of non invasive methods to determine the components of arterial impedance in order to evaluate the hemodynamic changes due to high blood pressure.

Arteries↗
PubMed1997

Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse.

Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous females were sterile owing to a complete failure of embryonic implantation. Moreover, they presented multiple reproductive abnormalities, including irregular cycles, reduced fertilization rates, defective preimplantation embryonic development, and lack of pseudopregnancy. Half of the homozygous males were infertile or showed reduced fertility. This work establishes the prolactin receptor as a key regulator of mammalian reproduction, and provides the first total ablation model to further study the role of the prolactin receptor and its ligands.

Animals↗
PubMed1997

The expanded Hansen approach to solubility parameters. Paracetamol and citric acid in individual solvents.

In this study two solubility-parameter models have been compared using as dependent variables the logarithm of the mole fraction solubility, lnX2e, and ln(alpha)/U (originally used in the extended Hansen method), where alpha is the activity coefficient and U is a function of the molar volume of the solute and the volume fraction of the solvent. The results show for the first time the proton-donor and -acceptor hydrogen-bonding capacities of paracetamol, as measured by the acidic and basic partial-solubility parameters. The influence of solvents on the differential scanning calorimetry (DSC) pattern of the solid phases was also studied in relation to the solubility models tested. Citric acid was chosen as a test substance because of its high acidity and its proton donor capacity to form hydrogen bonds with basic solvents. The partial acidic and basic solubility parameters obtained from multiple regression were consistent with this property, validating the model chosen. The results show that the more direct lnX2e variable was more suitable for fitting both models, and the four-parameter model seemed better for describing the interactions between solvent and solute.

Acetaminophen↗
PubMed1996

Transgenic mice expressing the Sh ble bleomycin resistance gene are protected against bleomycin-induced pulmonary fibrosis.

Despite the high efficiency of bleomycin (BLM) as a chemotherapeutic agent against various carcinomas, the potentially lethal and chronic fibrotic response of the lung is a major dose-limiting side effect. Here, we explore the possibility of a direct inhibition of lung tissue injury by in vivo expression of the actinomycetes BLM resistance protein Sh ble. Transgenic mice expressing the Sh ble gene under the control of a composite viral promoter were produced after introduction of the transgene into D3 ES cells. The protein was detected at high level in lungs, spleen, and kidney. We then assessed its ability to modulate the BLM-induced fibrotic response in the transgenic mice in comparison with C57BL/6 and 129/Sv parental mice. Cumulative doses of 300, 400, or 500 mg/kg BLM were administered either by i.p. or s.c. repeated injections in the different strains. Transgenic mice were shown to be clearly less sensitive to BLM toxicity, as assessed by lung histology. The pulmonary hydroxyproline content in the treated transgenic mice was close to its baseline level, whereas it was up to 50% higher than the control level in C57BL/6 and 129/Sv parental mice. These observations are consistent with the hypothesis that a resistance gene specifically expressed in lungs may prevent the BLM-induced inflammation.

Acetyltransferases↗
PubMed1996

Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome.

HNF1 is a transcriptional activator of many hepatic genes including albumin, alpha1-antitrypsin, and alpha- and beta-fibrinogen. It is related to the homeobox gene family and is predominantly expressed in liver and kidney. Mice lacking HNF1 fail to thrive and die around weaning after a progressive wasting syndrome with a marked liver enlargement. The transcription rate of genes like albumin and alpha1-antitrypsin is reduced, while the gene coding for phenylalanine hydroxylase is totally silent, giving rise to phenylketonuria. Mutant mice also suffer from severe Fanconi syndrome caused by renal proximal tubular dysfunction. The resulting massive urinary glucose loss leads to energy and water wasting. HNF1-deficient mice may provide a model for human renal Fanconi syndrome.

Animals↗
PubMed1996

Unexpected behavior of a gene trap vector comprising a fusion between the Sh ble and the lacZ genes.

A new gene trap vector has been designed, comprised of a fusion between the Sh ble gene, which confers resistance to the antibiotic phleomycin, and the lacZ gene (phleal fusion gene). A synthetic splice acceptor, made of the yeast branchpoint followed by a pyrimidin-rich sequence of 27 nucleotides, is included at the 5' extremity. The linearized gene trap vector was introduced into mouse embryonic stem cells (ES cells), and 40 phleomycin resistant (phleo') cell lines possessing a single copy of the insert were selected. They were stable in expressing the lacZ gene. Reporter gene expression was studied at days 8.5 and 10.5 of embryonic development in chimeric embryos obtained after injection of phleo' ES clones into 8-cell stage embryos. Out of 20 phleal lines examined, 14 exhibited beta-galactosidase expression at day 10.5. Use of the phleal fusion gene trap vector to select genes expressed in ES cells, therefore, is compatible with the isolation of genes expressed at midgestation. However, and most intriguingly, 10 out of these 14 cell lines (71%) displayed reporter gene expression mostly in heart and liver. Two of them exhibited, in addition, expression in central nervous system (CNS) or in CNS and limb buds, respectively. Germline chimeras were subsequently obtained and 15 mouse lines have been established. Intercrosses of animals heterozygous for the insertion revealed a mutant phenotype in several lines.

Animals↗
PubMed1996

Influence of surface free energies and cohesion parameters on pharmaceutical material interaction parameters-theoretical simulations.

PURPOSE: The aim of this study was to perform simulations of the influence of surface free energies and cohesion parameters on various interaction parameters within binary systems. METHODS: Using predictive equations derived from surface free energies and cohesion parameters originally proposed by Wu (2, 3) and by Rowe (4), values of interfacial tension, spreading and reduced spreading coefficients, interaction parameter and strength of interaction were simulated by means of a data processor. The influence of polar and disperse fractions of the two interacting materials was also examined. RESULTS: From the simulations, boundary conditions could be drawn: minimum interfacial tension, positive spreading coefficient, reduced spreading coefficient superior to unity, maximum value of the interaction parameter or of the strength of interaction. CONCLUSIONS: Simulations of the various parameters will help the formulator to select proper materials, eg. an agent that will efficiently bind some powdered substrate, a film-forming agent that will properly coat given cores or a material that will enhibit high interaction with a substrate.

Biocompatible Materials↗
PubMed1995

Effects of hypertension on viscoelasticity of carotid and femoral arteries in humans.

We compared the properties of common carotid and femoral arteries of 16 normotensive and 14 hypertensive men. Arterial pressure and diameter were recorded noninvasively in each vessel by tonometric and echotracking devices. The x-y composition of pressure and diameter waves provided the diameter-pressure hysteresis loop. The elastic diameter-pressure curve and wall viscosity index were deduced after hysteresis elimination. The compliance-pressure and distensibility-pressure curves were derived from the diameter-pressure curve, allowing the calculation of effective compliance and distensibility at the prevailing pressure of each subject and isobaric compliance and distensibility at the same standard pressure in all subjects. Systolic, diastolic, mean, and pulse pressures and diameters in each vessel were higher in the hypertensive than the normotensive group, except carotid pulse diameter, which did not differ. The carotid diameter-pressure, compliance-pressure, and distensibility-pressure curves did not differ between groups. In the carotid artery hypertensive patients had isobaric compliance and distensibility values similar to those of normotensive subjects, despite lower effective compliance (P < .05) and distensibility (P < .01). The femoral diameter-pressure curve was higher (P < .05) and the femoral compliance-pressure and distensibility-pressure curves were lower (P < .01) in the hypertensive than the normotensive group. Hypertensive patients had effective and isobaric femoral compliance and distensibility values lower than to those of normotensive subjects (P < .001). In both arteries, viscosity index was higher in the hypertensive than the normotensive group (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

High-performance liquid chromatographic assay for the simultaneous determination of ethyl clofibrate and clofibric acid in plasma. Evaluation of plasma stability of ethyl clofibrate polylactic nanocapsules in human and rat plasmas.

A rapid, sensitive, and selective HPLC assay was developed for the simultaneous determination of ethyl clofibrate and its major metabolite, clofibric acid, in plasma of humans and rats. The assay involves extraction of the compounds into chloroform-isoamyl alcohol (99:1, v/v) from plasma acidified with sulfuric acid. For human plasma, the overall recoveries of ethyl clofibrate and clofibric acid were 63 and 90%, respectively. The limits of detection of the assay for ethyl clofibrate and clofibric acid in human plasma were 1.1 and 1.5 micrograms/ml, respectively. Limits of quantitation of the assay for ethyl clofibrate and clofibric acid in human plasma were 3.6 and 4.9 micrograms/ml, respectively. The HPLC assay was used to monitor the plasma concentration-time profiles of ethyl clofibrate released from polylactic nanocapsules both in man and rat. The simultaneous determination of ethyl clofibrate and clofibric acid provided evidence that these colloidal systems are stable in human plasma whereas they are lysed in rat plasma.

Animals↗
PubMed1994

[Permanent cardiac stimulation after aortic valve replacement: incidence, predictive factors and long-term prognosis].

Between January 1981 and June 1992, 382 patients, operated by the same surgical team, underwent aortic valve replacement for pure severe aortic stenosis. This population was divided into 2 groups according to whether or not surgery was complicated by the development of a conduction defect (atrioventricular and/or intraventricular block), necessitating permanent cardiac pacing. The aim of this study was to analyse not only the incidence and predictive factors but also the long-term prognosis of the paced patients (Group II: 22 patients) in comparison with the control group (Group I: 360 patients). The results showed: the incidence of permanent cardiac pacing after this type of surgery remains low (5.7%); the predictive factors of atrioventricular block requiring permanent pacing were: pre-existing conduction defect (p < 0.02), decreased ejection fraction (p < 0.05), calcification extending to the subaortic interventricular septum (p < 0.0001); the long-term prognosis of the patients was good with 5 and 10 year actuarial survival rates of 95.4% and 68.9% respectively, identical to those of the control group.

Actuarial Analysis↗
PubMed1991

Participation of the paternal genome is not required before the eight-cell stage for full-term development of mouse embryos.

Differential expression of the paternal and maternal genomes during mouse embryonic development is considered a reason for both genomes being required for development to term. Extending previous studies performed on two-cell embryos, we show here that diploid embryos reconstituted at the four-cell stage from uniparental haploid blastomeres can produce living offspring. This result shows that for normal development to occur, a paternal genome does not need to be associated with a maternal genome within the same nucleus before the eight-cell stage.

Animals↗
PubMed1990

Effects of muscarinic and beta-adrenergic blockade on the aortic elastic response to epinephrine induced acute hypertension in conscious dogs.

To determine the effects of parasympathetic blockade and beta-blockade on the elastic response of aortic stiffness to vasopressive interventions, we studied 5 unanesthetised adult mongrel dogs by means of a pressure microtransducer and two ultrasonic crystals positioned at opposing sites in the proximal descending thoracic aorta which were used for diameter measurements. Systolic and diastolic changes in pressure and diameter were used to calculate Peterson and incremental elastic moduli. Acute hypertension was induced using infusions of epinephrine during the control period and later propranolol (1.5 mg/kg) plus atropine (0.2 mg/kg). Percent variations of mean aortic diameter were correlated to percent variations in mean aortic pressure in the control period and after autonomic blockade (P less than .001). The slopes of these correlations in the control group were higher than after autonomic blockade (P less than .05). Correlations were also found between Peterson and incremental elastic moduli and mean pressure in the control group and after autonomic blockade (P less than .001). The slopes of the correlations of incremental elastic modulus and Peterson's modulus versus mean aortic pressure were lower in the control group than after blockade (P less than .001). We conclude that in conscious dogs, autonomic blockade with propranolol and atropine decreased the distension and increased the stiffness of the aortic wall in response to acute hypertension mediated by epinephrine.

Acute Disease↗
PubMed1988

Aortic pulsatile pressure and diameter response to intravenous perfusions of angiotensin, norepinephrine, and epinephrine in conscious dogs.

The aortic elastic behavior has been studied in conscious dogs chronically instrumented with a pressure microtransducer and two ultrasonic crystals. Pressure and diameter measurements were analyzed in terms of their mean values and systolic-diastolic variations, enabling calculation of Peterson elastic modulus, and were displayed in the x-y form to obtain pressure diameter hysteresis loops. After recovery from surgery and under autonomic blockade, intravenous perfusions of angiotensin, norepinephrine, and epinephrine were made at incremental steps of doses until steady-state pressure-diameter changes were achieved. The slopes of the positive pressure-diameter correlations obtained at each dose of the same vasoactive substance were higher for angiotensin than norepinephrine (p less than 0.01) and epinephrine (p less than 0.001) and were higher for norepinephrine than epinephrine (p less than 0.05). Similarly, the slopes of the elastic modulus to mean pressure relation were significantly lower for angiotensin than for norepinephrine (p less than 0.05) and epinephrine (p less than 0.001) and were significantly lower for norepinephrine than epinephrine (p less than 0.001). Thus, at the same transmural pressure, the distension and stiffness of the aorta were lower and higher with epinephrine than with norepinephrine, respectively, and with norepinephrine than with angiotensin suggesting different potencies of these drugs in terms of smooth muscle activation in the aorta.

Angiotensin II↗
PubMed1988

Constricting and stiffening action of atropine on aortic response to angiotensin in dogs.

The elasticity of the thoracic aorta was studied in nine dogs instrumented with a pressure microtransducer and two ultrasonic crystals diametrically fixed in the adventitia. Systolic and diastolic changes in pressure and diameter were used to calculate Peterson and incremental elastic moduli. Acute hypertension was induced by infusions of angiotensin performed 1) during the control period, 2) after propranolol (1.5 mg/kg), 3) after atropine (0.2 mg/kg), and 4) after propranolol plus atropine. Absolute and percent variations of mean diameter were correlated to pressure in the control period and after autonomic blockade (p less than 0.01). The slopes of these correlations were not different between propranolol and control groups, but were lower with atropine (p less than 0.01) and with atropine plus propranolol (p less than 0.001) than in the control period. Correlations were also found between Peterson and incremental elastic moduli and mean pressure in the control period and after blockade (p less than 0.001). No differences of slopes existed between propranolol and control groups, but the slope of the correlation relative to the incremental elastic modulus was higher with atropine than in the control period (p less than 0.05), and the slopes of the correlations relative to the Peterson and the incremental elastic moduli were respectively higher with atropine plus propranolol than in the control period (p less than 0.05, p less than 0.05). Thus, atropine decreased the distention and increased the stiffness of the aorta in response to acute angiotensin-mediated hypertension.

Angiotensin II↗