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Biomedical subjects

A Santos

Publications and source records attributed to A Santos.

At least 91 records · Page 5Linked to original sources
PubMed2000

Influence of salt intake on the daytime-nighttime blood pressure variation in normotensive and hypertensive black subjects.

OBJECTIVE: To evaluate the influence of different salt-intake regimens on the circadian rhythm of blood pressure (daytime-night-time relationship) in normotensive and hypertensive black subjects with different patterns of salt sensitivity. METHODS: Randomized, cross-over study. Twenty normotensive (NT) and 27 hypertensive (HT) black subjects were kept on a low-sodium diet (30 mmol sodium/d, LS) and on a high-sodium diet (300 mmol sodium/d, HS) for 1 week each. On the last day of each regimen, 24 hour ambulatory blood pressure monitoring was performed. RESULTS: Eight normotensives were classified as salt-sensitive (SS), all with haptoglobin phenotypes (FeHap) 1,1 or 1,2, and 12 as salt resistant (SR), 5 with FeHap 2,2. Seventeen hypertensives were classified as SS, all with FeHap 1,1 or 1,2, and 11 as SR, 2 with FeHap 2,2. Salt sensitivity criterium was: difference > 5 mmHg of 24 h mean blood pressure from low sodium to high sodium. The pattern of daytime-nighttime blood pressure relationship between LS and HS was only modified (respectively from dipper to non-dipper) in HT-SS, but not in NT-SS, NT-SR and HT-SR. The percentual drop in nighttime mean blood pressure was about 10% in HT-SR and in NT-SR either under LS or HS. In NT-SS, the percentual night-time drop in mean blood pressure was lower than that of NT-RS (i.e. about 7-8%), but it was not different on LS and on HS. In contrast, in HT-SS, the percentual nighttime drop in mean blood pressure on HS (6%) was significantly lower than that on LS (10%, p < 0.01). In the 27 HT, but not in the NT, changes in the nocturnal drop in mean blood pressure induced by salt restriction correlated positively with the degree of salt sensitivity (r = 0.45, p < 0.05). CONCLUSIONS: In black subjects, the pattern of nighttime-daytime blood pressure relationship appears to be modified from LS to HS diets (or vice-versa) only in SS hypertensive subjects, but neither in NT-SS nor in NT-SS and HT-SR. Only in HT-SS, but not in the other groups, salt restriction shifts the circadian rhythm of blood pressure from a non-dipper to a dipper pattern. We conclude that in black salt-sensitive hypertensives, salt restriction improves the circadian rhythm of blood pressure. This may have important therapeutic consequences on target organ damage associated with non-dipper patterns.

Adult↗
PubMed2000

Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans.

7-Ethyl-10[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin (CPT-11), a DNA topoisomerase I inhibitor, undergoes several metabolic pathways to generate conjugated and unconjugated derivatives that could be excreted from the body. The objective of this study was to determine the oxidative metabolites of CPT-11 recovered in human urine samples and to identify cytochrome P450 (CYP) involved in their formation. In addition to the already known metabolites of CPT-11 [SN-38, SN-38-G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC), and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin (NPC)], we isolated three oxidized metabolites from the urine of two children and two adults given CPT-11. M1 and M2 (molecular weight, 602) were hydroxylated, respectively, on the CPT moiety and on the terminal piperidine ring of CPT-11. M3 had a molecular mass of 602, but its urine concentration in patients was too low to establish its chemical structure by liquid chromatography/mass spectrometry. In vitro incubations with cells expressing CYP2C8, CYP2C9, CYP1A1, CYP1A2, or CYP3A7 did not produce any detectable metabolites. Only CYP3A4 produced both APC and NPC, resulting from the oxidation of the piperidinylpiperidine side chain of CPT-11 along with metabolite M2. The metabolism of CPT-11 by CYP3A5 was markedly different because neither APC or NPC nor M2 was produced, whereas only one new metabolite, M4 (molecular weight, 558), was generated by de-ethylation of the CPT moiety. No previous study has reported the presence of the M4 metabolite. Production of APC, NPC, M2, and M4 was prevented by ketoconazole, a specific CYP3A inhibitor. The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4. In conclusion, CYP3A plays a major role in the metabolism of CPT-11, with some differences of the metabolic profile exhibited by 3A4 and 3A5.

Adolescent↗
PubMed1999

Involvement of the NGFI-A gene in the differentiation of neuroblastoma cells.

The transcription factor NGFI-A is an early response gene that has been implicated in the regulation of cell growth and differentiation and, more recently, in apoptosis. This gene is expressed in many tissues, and is very abundant in the brain. However, little is known about its functional role in the differentiation of this tissue. In the present work we investigated the role of NGFI-A in serum withdrawal-induced differentiation in N2A neuroblastoma cells. To do so, we studied the effect of NGFI-A antisense oligonucleotides and NGFI-A overexpression on this process. We show that neuroblastoma cells treated with an NGFI-A antisense oligonucleotide do not undergo normal morphological differentiation after serum withdrawal, whereas N2A cells overexpressing this gene extend long neurites, even in the presence of serum. We also show that NGFI-A overexpression is accompanied by an increase in the amount of phosphorylated microtubule-associated protein MAP1B, which has been associated with neurite outgrowth. Our results suggest that the NGFI-A gene plays an important role in neurite extension.

Animals↗
PubMed1999

RegulonDB (version 2.0): a database on transcriptional regulation in Escherichia coli.

RegulonDB version 2.0, a database on transcriptional regulation and operon organization in Escherichia coli, is now available on the web at the following URL: http://www.cifn.unam. mx/Computational_Biology/regulondb/. In this paper we describe the main computational changes to the database, which include migrating the database to Sybase, providing graphical descriptions of the internal organization of operons and regulons, and direct links to MEDLINE references. The web interface offers searching either by mechanisms of regulation or by operon organization. The results of a search (operon organization, or site collection) are displayed as hypertext, and can also be displayed graphically. In terms of its contents, RegulonDB contains a large number of operons, as well as the absolute position in the completed genome sequence of sites, promoters, and individual genes of E.coli.

Databases, Factual↗
PubMed1999

Differences in behavior profile between normotensive subjects and patients with white-coat and sustained hypertension.

It has been hypothesized that white-coat hypertensives (WCHs) have lower cardiovascular risk than sustained hypertensives (HTs), but higher emotional reactivity. We evaluated 92 HT patients (clinic and daytime BP>140/90 mmHg), 52 WCHs (clinic BP>140190 and ambulatory daytime BP<134/ 85 mmHg), and 74 normotensive subjects (NTs, clinic BP<140/90 and ambulatory daytime BP<134/85 mmHg), aged between 24 and 72 years, and matched for educational level, age, gender, and weight for depression, psychopathology, well-being, and quality of life. HTs showed worse scores than WCHs and NTs on most of the psychological variables; no differences were found between WCHs and NTs except on physical mobility. Daytime BP variability was HTs>WCHs>NTs, whereas nighttime BP variability was HTs>WCHs=NTs. We conclude that HTs have worse psychological profiles than the other two groups. WCHs and NTs have similar psychological profiles, although WCHs have a higher daytime BP variability, which is not associated with higher emotional reactivity.

Adult↗
PubMed1999

Magnetic resonance imaging in the evaluation of inflammatory lesions in muscular and soft tissues: an experimental infection model induced by Candida albicans.

We have developed an experimental model to monitor inflammatory lesions in muscle and soft-tissues during the different stages of the disease by means of Magnetic Resonance Imaging (MRI). MRI of mice legs infected with Candida albicans was performed by standard two-dimensional spin echo and fast spin echo (RARE) using customized coils. The MRI findings were compared with pathologic examinations at the initial acute and established acute inflammatory stages, which provided accurate and detailed information on the evolution of the processes involved. The yeast caused inflammation within the first hours post-inoculation, appearing on T2-weighted images as an inhomogeneous mass with increased signal intensity. The presence of fungal hyphae was observed as hypointense signal areas in both T2 and T1 weighted images, with histologic confirmation. Areas of decreased signal intensity on T2 weighted images were apparent on the last experimental day and were attributed to the granulation tissue located within the capsule surrounding the abscess. The close correlation found between MRI and histopathology suggests that MRI is an ideal radiologic technique for monitoring the clinical and therapeutic follow-up of fungal infections in muscle and soft tissues.

Animals↗
PubMed1999

Atrioventricular septal defect following blunt chest trauma.

The authors describe an acquired atrioventricular septal defect that has resulted from a blunt chest trauma. Besides being an uncommon traumatic heart injury, this case has the particularities of the non-involvement of other adjacent anatomical structures and the long delay between the accident and the occurrence of the myocardial rupture.

Adolescent↗
PubMed1999

Turbutest in the training of asthmatic Turbuhaler users.

BACKGROUND: Correct utilization of inhalation devices is a key factor in asthma management. Objective assessment of the ability to use inhaler devices is therefore fundamental. METHODS: The objective was to assess objectively the inhalation technique of Turbuhaler users who reported having no difficulty in using such a device. A total of 600 asthmatic patients of our allergology outpatient department, daily users of Turbuhaler devices, were evaluated with Turbutest. This is a simple portable apparatus which connects a Turbuhaler inhaler with an electronic device to allow semiquantitative assessment of inhalation technique, with a score ranging from 0 (worst) to 3 (best), readily visualized on the apparatus. Patients were allowed to practice with Turbutest, assisted by an allergologist, until they improved their scores. A second Turbutest assessment was performed at a 2-month follow-up visit. RESULTS: On the first assessment, one-third of the patients had scores inadequate to allow a good inhalation, and only 20% achieved a score of 3. On the second assessment, significantly higher Turbutest scores were observed. CONCLUSIONS: Turbutest is a valuable tool in asthmatic patients' training, allowing identification and improvement of an inadequate inhalation technique with Turbuhaler.

Adult↗
PubMed1999

A mathematical model for toxin accumulation by killer yeasts based on the yeast population growth.

The accumulation of toxin by killer yeast populations is modelled starting from a mechanistic approach that explains the toxin production in terms of yeast population growth, and takes into account the environmental inactivation of the toxin. A modified Richard's general equation for limited growth is used to define the function that describes the toxin produced in relation to the yeast biomass increase. The relationship between the rates of cell and toxin production is explicitly shown, and the implications of the resulting proportionality factor are discussed. The model parameters have been adjusted and the model has been validated using experimental data of growth and toxin accumulation from cultures of Pichia membranaefaciens in two different media. The differences between both types of cultures are analysed on the basis of parameter estimates and the predicted rate of toxin production per cell. The results support the hypothesis that biomass production and toxin synthesis are controlled in different ways; they also suggest that the composition of the medium could have a distinct effect on toxin synthesis. Model assumptions are discussed in comparison with a previous model for killer-sensitive interaction of Saccharomyces cerevisiae strains.

Computer Simulation↗
PubMed1999

Proposed panel of diagnostic criteria, including the use of ultrasound, to refine the concept of 'endemic normals' in lymphatic filariasis.

Although living adult Wuchereria bancrofti worms can be detected by ultrasound examination of the scrotal area in approximately 80% of men infected with this filarial parasite, the location of the adult worms in the remaining 20% remains unclear. To determine this, 32 individuals who had W. bancrofti microfilaraemia but no adult worms detectable on ultrasound were treated with diethylcarbarmazine (DEC), either with a single 6 mg/kg dose (n = 13) or with a 12-day course of 6 mg/kg per day (n = 19). They were then monitored with serial physical and ultrasound examinations. Thirteen (41%) subjects developed small, single scrotal nodules 12 h to 7 days after treatment; this rate was unaffected by the dose of DEC. No nodules were detected outside the scrotal area. All 5 men with lymphangiectasia suspected on ultrasound before treatment developed scrotal nodules, compared to 8 (29.6%) of 27 men without ultrasonographic evidence (P = 0.006). Thus, using both ultrasound and 'provocative' treatment with DEC, adult W. bancrofti can be detected in the scrotal area of an estimated 88% of infected men. Because no single diagnostic test for W. bancrofti infection is completely sensitive, a panel of tests, including ultrasound, is proposed to identify with greater accuracy 'endemic normals' for immunological and epidemiological studies.

Adult↗
PubMed1999

The interaction of ancrod with human platelets.

Ancrod, a serine protease purified from the venom of Agkistrodon rhodostoma, has been used as a therapeutic anticoagulant for a number of indications, including replacement of heparin in patients with heparin-induced thrombocytopenia. Ancrod has similar fibrinolytic activity to thrombin, but ancrod specifically cleaves only the alpha chain of fibrinogen, producing the characteristic fibrinopeptides A, AP and AY. Because ancrod has been used in patients with heparin-induced thrombocytopenia, it is important to ensure that ancrod does not directly affect the platelets and potentially increase the hemostatic effect. The effect of ancrod on platelets has not been well established, and there is not agreement in published studies. Additionally, some of the studies are over 15 years old and pre-date sensitive assays such as glycoprotein analysis. For these reasons, we investigated the interaction of ancrod with human platelets using direct and indirect, functional and biochemical techniques. Incubation of platelets with ancrod alone did not induce platelet aggregation or the release of dense-granule contents. Pre-incubation of platelets with ancrod did not augment or inhibit the maximal aggregation achieved with thrombin, nor did it affect the amount of serotonin release from dense granules caused by activation by thrombin. Studies of ancrod-treated platelets using monoclonal antibody-mediated radioimmunoprecipitation demonstrated that high concentrations of ancrod did not cause measurable cleavage of either the glycoproteins Ib-IX or IIb-IIIa. Incubation of radiolabeled platelets with ancrod-treated plasma also had no effect on the platelet glycoproteins, indicating that ancrod does not indirectly affect the major surface receptors. Direct binding studies using radiolabeled ancrod did not demonstrate specific binding to the platelet surface. Together these studies indicate that ancrod does not directly affect nor bind to platelets in vitro. The hypo-coagulant state and subsequent platelet function defect resulting from the use of ancrod appears to be limited to the removal of fibrinogen from the circulation.

Journal Article↗
PubMed1999

Deficiency of renal dopaminergic-dependent natriuretic response to acute sodium load in black salt-sensitive subjects in contrast to salt-resistant subjects.

OBJECTIVE: To evaluate the involvement of the renal dopaminergic system in the natriuretic responses to acute saline load in salt-resistant (SR) and salt-sensitive (SS) black normotensive (NT) and hypertensive (HT) subjects. DESIGN AND METHODS: We studied the relationship between the urinary excretion of dopa, dopamine (DA) and its metabolite DOPAC and the natriuretic responses to acute volume expansion (2 l NaCl 0.9% over 2 h) in 20 black NT subjects (12 SR and 8 SS) and 19 black HT subjects (10 SS and 9 SR). Subjects received a low salt (LS) diet (40 mmol sodium/day) for 1 week and a high salt (HS) diet (300 mmol sodium/day) for 1 week; the sequence of the dietary regimens was randomized. Comparisons were made between the results before the saline infusion (baseline) and the results 2 h after the infusion. RESULTS: In all the groups saline infusion induced significant increases in urinary volume (ml/4 h) of two- to three-fold and in urinary sodium excretion (mmol/4 h) of three- to ten-fold; these increases were significantly greater during the HS diet than during the LS diet. Saline infusion significantly increased the mean arterial pressure (MAP) by 5 mmHg in HT-SS subjects and by 4-5 mmHg in NT-SS subjects, but the MAP did not changed in the NT-SR and HT-SR groups. Under the LS diet, saline infusion changed the DA excretion (in nmol/4 h) by -49+/-89 in HT-SS subjects, by 17+/-52 in NT-SS subjects, by 235+/-72 in HT-SR subjects and by 220+/-86 in NT-SR subjects (P < 0.05 between SR and SS subjects). The saline infusion-induced changes in DA excretion correlated significantly with the increases in urinary sodium excretion (r = 0.71, P < 0.01) in the NT-SR and HT-SR subjects under the LS diet, but not in the SR groups on the HS diet nor in the SS groups (HT and NT) on either diet. Saline infusion significantly reduced the DA/dopa ratio in SS (NT and HT) but not SR (NT and HT) subjects, whereas the DA/DOPAC (dihydroxyphenylacetic acid) ratios were similar in all the groups. CONCLUSIONS: The urinary dopaminergic system may participate in the natriuretic responses to acute sodium load only in SR subjects (NT and HT) and only under LS diets, but not in SS subjects (NT and HT). This strongly suggests that black NT- and HT-SS subjects have an underlying impairment in the activity of the renal dopaminergic system which may be associated with a reduced decarboxylation of dopa into DA.

Adult↗
PubMed1999

Acute hypotensive, natriuretic, and hormonal effects of nifedipine in salt-sensitive and salt-resistant black normotensive and hypertensive subjects.

In a randomized double-blind study, we compared the short-term effects of nifedipine (10 mg 3x daily for 1 day) versus placebo on 24-h blood pressure, diuresis, natriuresis, urinary excretion of dopamine and metabolites, and on plasma renin activity (PRA) and plasma aldosterone levels in 18 black hypertensive (HT) patients [eight salt-resistant (HT-SR) and 10 salt-sensitive (HT-SS)], and in 20 black normotensive (NT) subjects (12 NT-SR and eight NT-SS) who were studied randomly with both a high- (HS) and a low-salt (LS) diet. In comparison to placebo, nifedipine significantly decreased 24-h mean BP in all groups either with HS or LS diets (all p<0.05). With HS, greater hypotensive effects were achieved in NT-SS (-10+/-2 mm Hg) versus NT-SR (-3+/-1 mm Hg; p<0.05) and in HT-SS (-18+/-2 mm Hg) versus HT-SR (-12+/-2 mm Hg; p<0.05). In NT-SS and HT-SS, nifedipine induced greater (p<0.05) BP decrease with HS (-10+/-2 and -18+/-2 mm Hg) than with LS (-4+/-1 and -9+/-1 mm Hg, respectively), whereas in NT-SR and HT-SR, the hypotensive effect did not differ between HS and LS. Nifedipine versus placebo significantly increased natriuresis and fractional excretion of sodium in all groups only with HS (p<0.05) but not with LS diets. Only in HT-SS were the hypotensive and natriuretic effects of nifedipine significantly correlated (r = -0.77; p<0.01). Nifedipine produced a similar increase of the urinary excretion of dopamine, L-DOPA, and of DOPAC in all subjects, which did not correlate with hypotensive and natriuretic effects. Nifedipine did not modify plasma levels of renin and of aldosterone except in NT-SS with HS, in whom nifedipine increased PRA levels (p <0.05). We conclude that although nifedipine reduces BP in all groups of NT and HT with LS and HS diets, the effect is greater in salt-sensitive subjects with HS. Although in HT-SS with HS, the short-term natriuretic response to nifedipine may contribute to its hypotensive effects, the diuretic-natriuretic effect of nifedipine is not necessary for the expression of its hypotensive effect. Moreover, it is unlikely that any short-term effects of nifedipine either on the renal dopaminergic system or on the secretion of aldosterone explain nifedipine short-term hypotensive and diuretic-natriuretic effects.

Adult↗
PubMed1999

Diffusion in lattice Lorentz gases with a percolation threshold.

A mean-field approximation for the diffusion coefficient in lattice Lorentz gases with an arbitrary mixture of pointlike stochastic scatterers in the low-density limit is proposed. In this approximation, the diffusion coefficient is directly related to the first return probability of the moving particle in the corresponding Cayley tree through an effective ring operator. A renormalization scheme for the approximate determination of the first return probability is constructed. The predictions of this mean-field theory and those of the repeated ring approximation (RRA) are compared with computer simulation results for models in which a fraction x(B) of the scatterers are deterministic backscatterers, so that the diffusion coefficient vanishes beyond a certain percolation threshold x(c)(B). The approximation proposed in this paper is seen to be in good agreement with the simulation results, in contrast to the RRA, which already fails to give the correct percolation threshold.

Journal Article↗
PubMed1999

Simple and accurate theory for strong shock waves in a dense hard-sphere fluid.

Following an earlier work by Holian et al. [Phys. Rev. E 47, R24 (1993)] for a dilute gas, we present a theory for strong shock waves in a hard-sphere fluid described by the Enskog equation. The idea is to use the Navier-Stokes hydrodynamic equations but taking the temperature in the direction of shock propagation rather than the actual temperature in the computation of the transport coefficients. In general, for finite densities, this theory agrees much better with Monte Carlo simulations than the Navier-Stokes and (linear) Burnett theories, in contrast to the well-known superiority of the Burnett theory for dilute gases.

Journal Article↗