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Biomedical subjects

M A Ruiz

Publications and source records attributed to M A Ruiz.

At least 19 recordsLinked to original sources

Ftorafur loading and controlled release from poly(ethyl-2-cyanoacrylate) and poly(butylcyanoacrylate) nanospheres.

In the present work, a method is described to prepare polymeric colloidal nanospheres, consisting of poly(ethyl-2-cyanoacrylate) (PE-2-CA) or poly(butylcyanoacrylate) (PBCA), loaded with the anticancer drug ftorafur. The method is based on the anionic polymerization procedure, often used in the synthesis of poly(alkylcyanoacrylate) nanospheres for drug delivery. A detailed investigation of the capabilities of both polymeric nanoparticles to load this drug is shown. The effect of synthesis residuals and degradation products on the absorbance of supernatants was considered in the loading and release measurement methodologies, because of their potential perturbing influence on the determination of ftorafur concentration in solution. We found the existence of two mechanisms of drug incorporation: absorption or entrapment in the polymeric network, and surface adsorption, detectable by means of zeta potential and spectrophotometric measurements. Among the factors affecting the drug incorporation to the polymer network, the type of polymer, the pH and the drug concentration are the main determining ones. Moreover, the acidity of the medium needs to be controlled in order to avoid the formation of macroaggregates of solids. The optimum loading conditions were used to perform ftorafur release evaluations from polymeric particles, and the influence of the mechanism of drug incorporation, the amount of drug loaded, and the type of polymer on the drug release were studied.

Absorption↗

Asthma control in Spain. Do season and treatment pattern matter? The ESCASE study.

The aim of this study was to assess the degree of asthma control according to GINA criteria during two different seasons in Spain. An multicenter, longitudinal, epidemiological study with the participation of a sample of physicians in Spain was conducted. Consecutive asthma patients, 18 years of age and older, seeking primary and specialist care were included in the study. Patients were seen during the winter and spring 2004 and were asked about asthma control according to GINA control criteria (daytime and nighttime symptoms, asthma exacerbations, limitations of physical activity, and visits to the emergency department) during the 4 weeks prior to the visit. Control was defined according to daytime and nighttime symptoms. A total of 614 patients participated in the study. The proportion of patients reporting daytime symptoms "every day" or "most days" during the winter versus spring was 40.1% vs. 23% (P<0.01); 26.9% vs. 14.1% presented symptoms at night (P<0.01); 11.5% vs. 8.3% had severe exacerbations; 33.5% vs. 35.7% presented symptoms accompanying exercise, and 9.4% vs. 4.3% (P<0.01) had required emergency visits. The number of patients with inadequate control was slightly higher in winter than in spring (74.4% vs. 71%) (P<0.01). The most commonly prescribed treatment was ICS plus LABAs for both periods. Asthma is poorly controlled in Spain and strategies are needed to improve management of this illness.

Adolescent↗

Chemical characterization with XPS of the surface of polymer microparticles loaded with morphine.

Hydrophilic matrices are a potentially useful option for the development of oral controlled-release formulations. The porous surface of these particles makes it possible to control or modify release of the active principle after administration. As a result, such formulations can be used in liquid controlled-release pharmaceutical formulations. We investigated a method of spontaneous drug encapsulation to prepare ethylcellulose polymer microparticles (since the polymer is synthetic rather than natural the final suspension is called pseudolatex) filled with morphine hydrochloride. Morphine is incorporated to water during the synthesis process and thus it is microencapsulated inside the micelles that give rise to the final microparticles. X-ray photoelectron spectroscopy (XPS), a technique that can identify elements in a sample without destroying it, was used for the chemical analysis of the surface of these microspheres. The results demonstrated the complete absence of morphine from the microsphere surface, which was taken as evidence that the drug had been completely encapsulated.

Analgesics, Opioid↗

Chronic intake of caffeine during gestation down regulates metabotropic glutamate receptors in maternal and fetal rat heart.

Caffeine is the most widely consumed substance in the world which antagonizes adenosine effects. Adenosine acting through A(1) receptors inhibits glutamate release which binds to metabotropic glutamate receptors (mGluRs). Recently, we have shown that maternal caffeine intake during gestation causes down-regulation of A(1) and metabotropic glutamate receptors in the brain of both rat mothers and fetuses. In the present work we provide evidence that caffeine also affects receptors in hearts, causing a decrease in mGluRs from both maternal and fetal hearts. A decrease in G(q/11) and PLC beta(1) proteins level was also observed in both tissues. However, phospholipase C activity was only affected in fetal heart, being significantly decreased. These results suggest an in vivo cross-talk mechanism between adenosine and glutamate receptors in peripheral tissues. Therefore, special attention should be paid to caffeine ingestion during gestation.

Animals↗

Classification and scoring systems in myelodysplastic syndromes: a retrospective analysis of 311 patients.

The main objective of this study was to evaluate the role of the recent World Health Organization (WHO) classification for assessing prognosis in patients with myelodysplastic syndromes (MDS). To this effect, we analyzed the prognostic impact of the WHO and French-American-British (FAB) morphologic classifications and of four different scoring systems in a series of 311 patients with primary MDS diagnosed between October 1990 and June 2001. Both the FAB and WHO classifications identified groups with different prognoses (p<0.0001), those presenting refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) showing the best prognosis. The WHO classification subdivided RA into RA with only red cell dysplasia, and refractory cytopenia with multilineage dysplasia (RCMD), and RARS into RARS plus refractory cytopenia with multilineage dysplasia and ringed sideroblast (RCMD-RS). In our population, we have shown that the two subtypes characterized by dysplasia affecting exclusively the erythroid population (RA and RARS) have a better prognosis, with a median survival of 122.2 and 81.9 months, respectively, than those with multilineage dysplasia (RCMD and RCMD-RS) with a median survival of 32.3 and 43.2 months, respectively. There were no significant differences in median survival comparing RA with RAS (p<0.95), or comparing RCMD with RSCMD (p<0.97). Besides, the four scoring systems discriminated our MDS patients in terms of survival, and an increase in prognostic capacity was achieved on adding the score to the morphological classifications. Risk scoring had a greater prognostic impact than the FAB and WHO classifications. Prognostic scoring systems may be an important tool for risk stratification in hematological practice, and add significance to morphological classification. Combined application of the WHO classification and score system is useful for improving the identification of patients with a poorer prognosis. The WHO classification establishes more homogeneous subcategories than the FAB classification and is also able to identify groups with different prognoses.

Adult↗

Cross-cultural study comparing the association of familism with burden and depressive symptoms in two samples of Hispanic dementia caregivers.

Familism has been pointed out as a key value in Hispanic culture that may or may not be associated with caregiver distress. Although groups included in the Hispanic identity have many common features, differences between Hispanic sub-groups in the relationship of familism with burden and depressive symptoms remain unexplored. The association of familism with burden and depressive symptomatology was examined in 48 Hispanic dementia caregivers from Los Angeles (CA, USA) and 60 from Madrid (Spain) through path analyses. Burden and depressive symptomatology were positively and significantly related in both samples. Familism was significantly correlated with lesser burden in the USA Hispanic caregiver sample, but with higher levels of depressive symptoms in the Spanish sample. Significant differences between Hispanic samples were found in the relationship between familism, burden, and depression, denoting the importance of specific cultural contexts influencing dementia caregiving in Hispanics.

Aged↗

Frontline therapy with early intensification and autologous stem cell transplantation versus conventional chemotherapy in unselected high-risk, aggressive non-Hodgkin's lymphoma patients: a prospective randomized GEMOH report.

This prospective multicenter randomized trial compares conventional with early intensification with high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation (ASCT) as frontline therapy in high-risk non-Hodgkin lymphomas (NHL). Newly diagnosed patients with aggressive high-risk [intermediate-high (HI) and high-risk (HR)] NHL according to the international prognosis index (IPI) were randomized to receive 12-week VACOP-B (arm A, 27 patients) or 6-week VACOP-B followed by HDS and ASCT (arm B, 29 patients). Complete remission rate was 52% in arm A and 55% in B. Nine patients (16%) died early due to progression. According to intention-to-treat, with a median follow-up of 23 months, the 5-year actuarial overall survival, progression-free survival and disease-free survival in arms A and B were 47 and 40% (p = nonsignificant), 47 and 30% (p = nonsignificant), and 97 and 47% (p = 0.02), respectively. Abbreviated chemotherapy followed by intensification with HDS-ASCT does not seem to be superior to conventional chemotherapy in HI/HR aggressive NHL.

Adolescent↗

Effect of chronic glutamate administration to pregnant rats during gestation on metabotropic glutamate receptors from mothers and full-term fetuses brain.

Chronic glutamate treatment during gestational period caused a significant decrease in total metabotropic glutamate receptors (mGluR) number. Similar results were observed on the steady-state level of mGlu(1) receptor detected by immunoblotting assays, suggesting that this is the main receptor subtype modulated by agonist exposure. Furthermore, no variations on mRNA coding mGlu(1) receptor were found, suggesting post-transcriptional modulation as a possible mechanism of the lost of receptor detected at the membrane surface. On the other hand, western-blotting to determine level of G(q/11) protein and phospholipase C beta(1) revealed a significant decrease of both proteins in mothers brain. This decrease was associated with significant variation in glutamate and DHPG-stimulated phospholipase C activity. No significant differences on mGluR transduction pathway components were observed in fetuses brain. These results suggest that glutamate intake during pregnancy causes a down-regulation of different proteins involved in glutamate response mediated by mGluR only in mothers brain without significantly affecting fetuses brain.

Administration, Oral↗

An experimental investigation of the stability of ethylcellulose latex: correlation between zeta potential and sedimentation.

This paper aims at explaining the experimental observations of the stability and redispersibility of an aqueous ethylcellulose latex through the electrokinetic characterization of the particles. The surface charge and the electrical double layer thickness play an essential role in the stability of the system, hence the need for a full characterization of the polymeric particles. The effect of both pH and ionic strength of the dispersion medium were investigated. It was found that at acid pH values the latex displays "delayed" or "hindered" sedimentation: in such conditions, the electrophoretic mobility and zeta potential are rather low, indicating a small electrokinetic charge on the particles. At alkaline pH, when the dissociation of ionizable surface groups must be complete, the zeta potential is high and negative. The electrostatic repulsion between polymer particles is responsible for the low sedimentation volume and poor redispersibility of the latex. The effect of NaCl and CaCl(2) concentration on both the zeta potential and stability of the latexes was also investigated: it was found that CaCl(2) has the greatest influence, yielding flocculated, easily re-dispersible systems when its concentration in the dispersion medium is high enough. There qualitative observations were ascertained by means of calculations of the potential energy of interaction between particles. In the case of NaCl solutions, a high and relatively wide potential energy barrier was predicted, that may prevent the particle aggregation. Above 5mM NaCl a shallow minimum in the potential energy curves must lead to the formation of aggregates. Similar results were found with CaCl(2) solutions, although in this case the secondary minima are deeper and appear at lower concentrations.

Calcium Chloride↗

Comparative study of morphine diffusion from sustained release polymeric suspensions.

In recent years, great efforts have been devoted to the design of drug delivery systems. Many polymeric excipients have been studied in order to make drug release fit the desired profiles. The aim of this work was to design a morphine oral suspension, as sustained release pharmaceutical formulations. To this end, two different ethylcellulose suspensions were prepared: one with the drug incorporated during synthesis (suspension A) so that the drug was inside the polymeric microparticles. In the second group of suspensions the drug was incorporated after synthesis (suspension B), thus resulting in the drug being adsorbed on the surface. The analytical technique used, spectrophotometry, showed that suspensions A were able to spontaneously encapsulate approximately 92% of the drug, whereas suspensions B adsorbed only 15% dose on the particle surface. Moreover, the diffusion results obtained with Franz-cells showed that suspensions A offered the possibility of easy control of the release rate of the active substance. This system transfers morphine hydrocloride during 24 h in accordance with a Weibull kinetic model. This dosage form presents the clinical advantage of less frequent dosing, with increased quality of life for patients. This report documents the suitability of our ethylcellulose polymeric suspension for encapsulated morphine with a controlled release rate.

Analgesics, Opioid↗

Electrophoretic properties of acrylic latex suspensions (Kollicoat MAE 30 D) and ibuprofen.

We have compared the electrophoretic properties (measured on the electrical surface) of the commercial latex Kollicoat MAE 30 D and the non-steroidal anti-inflammatory drug (NSAID) ibuprofen in preparation for attempts to develop a suitable vehicle for the NSAID to obtain a modified release formulation. Electrophoretic mobility of the latex and the active principle was measured in solutions containing different concentrations of inorganic electrolytes (NaCl, CaCl2 and AlCl3) at different pH values. This was considered an indispensable first step for further characterization of the substance's electrical properties. Suspensions of both the latex and the drug had negative mobility values throughout the range of pH values studied here. Of the electrolytes, neither NaCl nor CaCl2 led to positive mobility, and no isoelectric point could be determined. However, AlCl3 at a concentration of 10(-3) M led to the greatest reduction in mobility. We therefore found that trivalent cations were more effective than divalent cations, which in turn were more effective than monovalent cations, in reducing mobility.

Acrylates↗

Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection.

Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3-53 years, median 24) with aplastic anemia to reduce graft rejection. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine-methotrexate. The number of prior transfusions was 0-276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10 secondary rejection at 28-1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (>/=50 U) it was 43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was 56%; patients who received </=15 and >15 transfusions was 78 and 50%, respectively (P=0.01), whereas it was 67 and 28% for </=50 and >50 transfusions, respectively (P=0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to <50 transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients.

Adolescent↗

Uptake and distribution of zinc, cadmium, lead and copper in Brassica napus var. oleífera and Helianthus annus grown in contaminated soils.

Brassica napus var. oleifera and Helianthus annus were grown in artificially contaminated soils. Accumulation and translocation of the environmental pollutants zinc, cadmium, lead, and copper, was evaluated in different portions of the plants at two harvesting times. The distribution into the plants of these metal ions, as well as their capacity for contaminant phytoextraction and accumulation was assessed. For this purpose, an analytical method utilizing focused ultrasound employed for extraction and stripping voltammetry for measurement has been optimized and validated for the simultaneous measurement of Zn, Cd, Pb, and Cu in plant extracts.

Brassica napus↗

Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma.

Patients with mantle cell lymphoma (MCL) may present with either nodal or leukemic disease. The molecular determinants underlying this different biologic behavior are not known. This study compared the pattern of genetic abnormalities in patients with nodal and leukemic phases of MCL using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) for specific gene loci. Although both leukemic and nodal MCL showed similar genomic patterns of losses (involving 6q, 11q22-q23, 13q14, and 17p13) and gains (affecting 3q and 8q), genomic loss of chromosome 8p occurred more frequently in patients with leukemic disease (79% versus 11%, P <.001). Subsequent CGH analysis confirmed the genomic loss of 8p21-p23 in 6 of 8 MCL cell lines. Interestingly, MYC gene amplification was restricted to cases with 8p deletion. These data indicate the presence of a novel tumor suppressor gene locus on 8p, whose deletion may be associated with leukemic dissemination and poor prognosis in patients with MCL.

Chromosomes, Human, Pair 8↗

Eating disorders and altered eating behaviors in adolescents of normal weight in a Spanish city.

PURPOSE: To study the prevalence of altered eating behaviors or eating disorder-related behaviors among adolescents of normal weight that do not fulfill criteria for anorexia nervosa and bulimia nervosa. METHOD: Cross-sectional study by means of a self-completed questionnaire (School of Nutrition of Granada, Spain) and measurement of weight and height in a population of 491 schoolchildren aged 14-18 years. The statistical inferences and estimation of risk are based on comparison of proportions and means test, and the relative inequality of prevalences. RESULTS: Of 491 adolescents of normal weight, 9% (females 2:1) were following diets; 42% presented "recurrent episodes of binging" with the sensation of loss of self-control; and 41%% avoided specific types of food. Overall, 46.2% presented altered eating behavior. Factors significantly associated with this were the occurrence of periods of food abstinence and the use of purgatives [confidence interval 95% (CI 95%) prevalence ratio (PR) 1.41-2.02]. Compensatory behaviors were present in 33% of the adolescents, predominantly in females (CI 95% PR 1.79-3.07). The prevalences of abnormal eating behaviors were 16.3% for those related to anorexia (A-RB) and 17.1% for those related to bulimia (B-RB), with a clear predominance of females (2:1) and public education. There seems to be a greater aesthetic concern among those with B-RB and more worry about weight among those with A-RB. CONCLUSIONS: A high proportion of adolescents with abnormal eating behaviors and an altered perception of body fat may currently be diagnosed as having atypical eating disorder" (Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision) considering that their body mass index was within normal range.

Adolescent↗

Chemical composition, nutritive value, and toxicology evaluation of Mexican wild lupins.

The nutrient composition, toxic factors content, and nutritional and toxicological value of Lupinus splendens, L. rotundiflorus, L. elegans, L. simulans, L. exaltatus, L. reflexus, and L. madrensis species from Mexico were analyzed. The seeds of these species were a good source of protein. All the species showed a high lysine and tryptophan content, though sulfur amino acids were limiting. Cyanogenic glycosides were absent, and lectins, trypsin inhibitors, and tannins were present in low concentrations. Lupanine was the major alkaloid in almost all the samples, although sparteine was the major alkaloid in Lupinus reflexus (26.63 mg/g of sample). Cytisine was not found in any of the studied lupins. L. reflexus showed the highest acute toxicity, and L. elegans exhibited no toxicity as evaluated using a mice model. The alkaloid was reduced by hot-water extraction. The protein efficiency ratio in water-debittered seeds was relatively poor (1.1-1.5). These results suggest that the wild lupins studied represent a potential protein supply, and they could be domesticated and used for animal feed if the alkaloids were eliminated and the protein was supplemented with methionine, or if the lupins were used in mixture with cereals.

Evaluation Studies as Topic↗

X-ray diffraction and electron microscopy in the polymorphism study of ondansetron hydrochloride.

Using different techniques, we studied the possible formation of ondansetron polymorphs. Ondansetron is a carbazol antiemetic that acts as a competitive, selective inhibitor of 5-HT3 serotonin receptors. The polymorphs were determined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results suggest that the compounds are not true crystallographic polymorphs, but instead are the product of physical structural changes in the drug, which would be of interest pharmaceutically.

Algorithms↗