Biomedical subjects

M González

Publications and source records attributed to M González.

At least 19 recordsLinked to original sources

PubMed2007

Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age <or=40 and male gender were favorable variables for survival, whereas molecular response predicted longer leukemia-free survival. In conclusion, early institution of salvage therapy at molecular failure, before onset of hematological relapse, is beneficial in APL. Moreover, given the poor outcome of HEMrel managed with ATRA and HDAC, use of alternative therapeutic strategies in this setting is warranted.

Adolescent↗

PubMed2006

Design and evaluation of "3 + 1" mixed ligand oxorhenium and oxotechnetium complexes bearing a nitroaromatic group with potential application in nuclear medicine oncology.

The synthesis and evaluation of a series of oxotechnetium and oxorhenium complexes containing a nitroaromatic moiety as potential radiopharmaceuticals for targeting tumour hypoxia is presented. 99mTc labelling was performed in high yield (>85%) and radiochemical purity (>90%). Their structure was corroborated by means of the rhenium complexes. Reduction potentials were in the range for bioreducible compounds. 99mTc complexes III-VI were selected for "in vivo" experiments in view of the results of cytotoxicity studies. Biodistribution in normal animals was characterized by high initial blood, lung and liver uptake, fast blood and soft tissue depuration and preferential excretion via the hepatobiliary system. Initial tumour uptake was moderate but tumour/muscle ratios for complexes III and IV, were favourable at all time points. Although the results are encouraging further development is still necessary in order to achieve higher tumour uptake and lower gastrointestinal activity.

Animals↗

PubMed2006

Toxoplasma gondii: differential protection rates by two strains against cyst formation in a rat model.

A previous infection with the ME-49 strain of Toxoplasma gondii (of low pathogenicity for mice), protected 17 of 20 rats against formation of brain cysts, following challenge with 10(3) oocysts of the high pathogenicity M3 strain, as determined by bioassay of rat brains in mice. The low pathogenic KSU strain did not afford comparable protection. Protection was further tested in rats that were orally or subcutaneously immunized with cysts or oocysts of the ME-49 strain, and later challenged with 2 x 10(2) cysts or 10(2) oocysts of the highly pathogenic strains M3, M-7741 and C. Protection ranged from 43 to 100%, compared to non immunized control rats and was independent of the stage of ME-49 strain and of the routes used to immunize the rats. The results obtained encourage further investigation into prevention of toxoplasmosis in humans and food animals.

Animals↗

PubMed2006

Bisexual branching processes in a genetic context: the extinction problem for Y-linked genes.

In this paper the inheritance of a Y-linked gene with alleles R and r in a population with both females and males is modelled using a two-type bisexual branching process. It is assumed that the reproductive distribution associated with the R allele can differ from the associated with the r allele and that females prefer to mate with a male having the R allele rather than with a male with the r allele. Under these assumptions, we provide some conditions for the extinction and/or survival of both alleles in the population. These conditions depend on the magnitudes of the average number of females and males per mating unit. Moreover, the almost sure extinction of the r allele is independent of the behaviour of the R allele. On the other hand, the survival of the R allele with positive probability may depend strongly on the reproductive behaviour of the other allele. Theoretical results are illustrated by means of simulated examples and some open problems are proposed to the reader as conjectures.

Alleles↗

PubMed2006

Refinement of the mouse model of congenital toxoplasmosis.

The goals of the present investigation, focusing on the BALB/c mouse model of congenital toxoplasmosis, were: (1) to find a method to determine pregnancy in the mouse. The method has 100% sensitivity and 72% specificity; (2) to test congenital transmission during the chronic stage of toxoplasmosis. This occurred in 2 of 10 mice tested; (3) to investigate the relationship between the infective dose and the rate of congenital transmission. This was not demonstrated for doses of 10(2) to 10(3) bradyzoites and oocysts of Prugniaud, M3 and M7741 strains, with transmission rates of 3 of 8 to 6 of 10 mice inoculated; (4) to determine homologous and heterologous protection. Homologous protection was demonstrated with Prugniaud cysts, and heterologous protection was found between ME-49 and M3 cysts. This finding is consistent with the uniform natural protection against congenital toxoplasmosis seen in immune women and ewes.

Animals↗

PubMed2006

Sex steroid receptor expression in the oviduct and uterus of sheep with estrus synchronized with progestagen or prostaglandin analogues.

The objective of this study was to investigate differences in the expression of estrogen receptor-alpha (ERalpha), progesterone receptor (PR) and the proliferative indexes (Ki-67), in the uterus and oviduct of sheep with estrus synchronized either by prostaglandin analogues (Group PA, n=27) or by treatment with progestagens (Group P, n=29) on days 4 and 7 (day 0=estrus), when the embryos were collected. Immunohistochemical methods were used to quantify ERalpha, PR and Ki-67 in six superficial and deep compartments in the uterus and oviduct. The expression of ERalpha was significantly (P<0.01) lower in progestagen treated ewes than in prostaglandin analogues treated group in the luminal epithelium, superficial glands and superficial stroma in the uterus on day 4. The expression of PR was significantly lower in progesterone treated ewes than in the PA Group in the superficial gland (P<0.05) in both days studied. The lowest expression of PR was observed in the luminal caruncular epithelium and superficial glands in both treatments, obtaining the lowest levels on day 4 (P<0.05). There were significant differences between days 4 and 7 in the Ki-67 immunostaining in the luminal epithelium (P<0.01) and superficial glands (P<0.05). A higher cell proliferation was observed in the uterine epithelium (P<0.05) on day 4 in the animals treated with progestagens. Results indicate that sheep with synchronization of estrus with progestagens showed a reduction of ERalpha and PR protein expression in most of oviductal and uterine cells.

Animals↗

PubMed2006

Neuropharmacological effects of an ethanol extract of the Magnolia dealbata Zucc. leaves in mice.

Magnolia dealbata Zucc. is considered to have tranquilizer and anticonvulsant properties in Mexican traditional medicine. In the present study we report the effects of a crude extract of Magnolia dealbata (30, 100 and 300 mg/kg) on mouse central nervous system (CNS). Pharmacological effects were tested on ambulatory activity, anti-anxiety response, sodium pentobarbital-induced hypnosis and pentylenetetrazole (PTZ)-induced seizures in comparison to honokiol, buspirone, ethosuximide and diazepam as corresponding reference drugs. No changes in spontaneous locomotor activity were produced posterior to Magnolia dealbata administration; however, a significant and dose-dependent diminution in the anxiety response was observed in experimental models such as plus-maze, head-dipping and exploratory rearing tests. Magnolia dealbata not only prolonged the time of sodium pentobarbital-induced hypnosis and delayed the onset of PTZ-induced mioclonus and clonus, but also hindered the presence of tonic seizures and avoided mortality. The hypnotic, anxiolytic and anticonvulsant effects obtained in these experiments support the hypothesis that Magnolia dealbata possesses CNS activity and reinforces the popular use in Mexican traditional medicine.

Animals↗

PubMed2006

[Prognosis for acute exacerbation of chronic obstructive pulmonary disease in mechanically ventilated patients].

OBJECTIVE: To determine the variables associated with prognosis for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in mechanically ventilated patients. DESIGN: Prospective cohort study with retrospective analysis. LOCATION: 361 Intensive Care Units (ICU) in 20 countries. PATIENTS AND METHODS: There were included in the study 522 patients who required mechanical ventilation for more than 12 hours due to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In order to determine those variables associated with mortality, there was performed a recursive partition analysis in which the following variables were included: demographics, arterial blood gas prior to intubation, complications arising during mechanical ventilation (barotrauma, acute respiratory distress syndrome, ventilator-associated pneumonia, sepsis), organ dysfunction (cardiovascular, renal, liver, coagulation) and duration of ventilatory support. INTERVENTIONS: None. VARIABLES OF PRIME IMPORTANCE: ICU mortality. RESULTS: ICU and hospital mortality rates were 22% and 30%, respectively. Variables associated with mortality were cardiovascular dysfunction, renal dysfunction and duration of ventilatory support > 18 days. Median durations were as follows: mechanical ventilatory support, 4 days (P25: 2, P75: 6); weaning from ventilatory support, 2 days (P25: 1, P75: 5); stay in intensive care unit, 8 days (P25: 5, P75: 13); stay in hospital, 17 days (P25: 10, P75: 27). CONCLUSIONS: Mortality in the studied cohort of patients with AECOPD was associated with cardiovascular dysfunction, renal dysfunction and prolonged mechanical support.

Acute Disease↗

PubMed2006

Impact of highly active antiretroviral therapy on blood pressure in HIV-infected patients. A prospective study in a cohort of naive patients.

OBJECTIVES: To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. METHODS: A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) > or =140 mm Hg and/or diastolic BP (DBP) > or =90 mm Hg] was defined according to international criteria. RESULTS: Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. CONCLUSIONS: Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Phenazine 5,10-dioxide derivatives as hypoxic selective cytotoxins: Part II. Structure-activity relationship studies.

The synthesis and evaluation as hypoxic selective cytotoxins of new derivatives of 2-amino or 2-hydroxyphenazine 5,10-dioxide are described. The compounds were developed as structural analogs of other bioreductive compounds and its in vitro cytotoxicities on V79 cells under hypoxic and aerobic conditions were determined. To gain insight into its mechanism of action electrochemical behavior, interaction with DNA experiments and QSAR studies were performed.

Animals↗

PubMed2006

Furoxan derivatives as cytotoxic agents: preliminary in vivo antitumoral activity studies.

Furoxan derivatives with in vitro cytotoxic activity were investigated as antitumoral agents in vivo. The compounds were tested in murine models of both CCRFS-180 II sarcoma and mammary adenocarcinoma. Two of the furoxan derivatives considered here, 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide and 3-carbonitrile-4-phenyl-1,2,5-oxadiazole N2-oxide, present in vivo antitumoral activity. They were able to produce more than 90% of tumoral necrosis under the experimental protocol of administration and posology employed. NO-releasing capacity of furoxans may explain the anti-neoplastic activity of these compounds.

Animals↗

PubMed2005

Mercury and trace element fractionation in Almaden soils by application of different sequential extraction procedures.

A comparative evaluation of the mercury distribution in a soil sample from Almaden (Spain) has been performed by applying three different sequential extraction procedures, namely, modified BCR (three steps in sequence), Di Giulio-Ryan (four steps in sequence), and a specific SEP developed at CIEMAT (six steps in sequence). There were important differences in the mercury extraction results obtained by the three procedures according to the reagents applied and the sequence of their application. These findings highlight the difficulty of setting a universal SEP to obtain information on metal fractions of different mobility for any soil sample, as well as the requirement for knowledge about the mineralogical and chemical characteristics of the samples. The specific six-step CIEMAT sequential extraction procedure was applied to a soil profile (Ap, Ah, Bt1, and Bt2 horizons). The distribution of mercury and major, minor, and trace elements in the different fractions were determined. The results indicate that mercury is mainly released with 6 M HCl. The strong association of mercury with crystalline iron oxyhydroxides, present in all the horizons of the profile, and/or the solubility of some mercury compounds in such acid can explain this fact. Minor mercury is found in the fraction assigned to oxidizable matter and in the final insoluble residue (cinnabar).

Journal Article↗

PubMed2005

Genotoxicity of the herbicide 2,4-dichlorophenoxyacetic and a commercial formulation, 2,4-dichlorophenoxyacetic acid dimethylamine salt. I. Evaluation of DNA damage and cytogenetic endpoints in Chinese Hamster ovary (CHO) cells.

Genotoxicity of the 2,4-dichlorophenoxyacetic acid (2,4-D) and a commercially-used derivative, 2,4-D dimethylamine salt (2,4-D DMA), was evaluated in CHO cells using SCE and single cell gel electrophoresis (SCGE) assays. Log-phase cells were treated with 2.0-10.0 microg/ml of herbicides and harvested 24 and 36 h later for SCE analysis. Both agents induced significant dose-dependent increases in SCE, regardless of the harvesting time (2,4-D: r=0.98 and r=0.88, P<0.01, for 24 and 36 h harvesting times; 2,4-D DMA: r=0.97 and r=0.88, P<0.01, for 24 and 36 h harvesting times). Neither test compound altered cell-cycle progression or proliferative replication index (P>0.05), but the higher doses of both compounds reduced the mitotic index of cultures harvested at 24 and 36 h (P<0.05). A 90-min treatment with 2.0-10.0 microg/ml 2,4-D and 2,4-D DMA produced dose-dependent increases in the frequency of DNA-strand breaks detected in the SCGE assay, both in cultures harvested immediately after treatment and in cultures harvested 36 h later. The doses of 2,4-D and 2,4-D DMA were equally genotoxic in all of the assays. The results indicate that 2,4-D induces SCE and DNA damage in mammalian cells, and should be considered as potentially hazardous to humans.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2005

[Exhaled breath condensate: standardized collection of samples from healthy volunteers].

Expired breath condensate collection is a noninvasive technique for obtaining a sample in which to analyze substances that reflect the functional status of the lung and other tissues. Twenty healthy volunteers provided 3 expired breath samples: the second was collected 20 minutes after the first and the third 48 hours after the first. The air and condensate volumes were assessed. The mean (SD) volume of condensate in exhaled air over a period of 15 minutes was 1.8 (0.5) mL (95% confidence interval [CI], 1.5-2 mL) and the coefficient of variation was 29%. Analysis of variance in the 3 samples demonstrated no significant differences. The mean volume of air inhaled over 15 minutes was 119 (25) L (95% CI, 112-125 L). These results indicate that it takes at least 15 minutes and the inhalation of some 120 L of air to collect a condensate volume that exceeds 1.5 mL, sufficient to allow distribution in aliquots to analyze fundamental physical and chemical properties (conductivity, pH) and certain relevant biomarkers.

Adult↗

PubMed2005

Gene expression profile reveals deregulation of genes with relevant functions in the different subclasses of acute myeloid leukemia.

Bone marrow samples from 43 adult patients with de novo diagnosed acute myeloid leukemia (AML)--10 acute promyelocytic leukemias (APL) with t(15;17), four AML with inv(16), seven monocytic leukemias and 22 nonmonocytic leukemias--were analyzed using high-density oligonucleotide microarrays. Hierarchical clustering analysis segregated APL, AML with inv(16), monocytic leukemias and the remaining AML into separate groups. A set of only 21 genes was able to assign AML to one of these three classes: APL, inv(16) and other AML subtype without a specific translocation. Quantitative RT-PCR performed for 18 out of these predictor genes confirmed microarray results. APL expressed high levels of FGF13 and FGFR1 as well as two potent angiogenic factors, HGF and VEGF. AML with inv(16) showed an upregulation of MYH11 and a downregulation of a gene encoding a core-binding factor protein, RUNX3. Genes involved in cell adhesion represented the most altered functional category in monocytic leukemias. Two major groups emerged from the remaining 22 AML: cluster A with 10 samples and cluster B with 12. All the eight leukemias that were either refractory to treatment or that relapsed afterwards were assigned to cluster B. In the latter cluster, CD34 upregulation and serine proteases downregulation is consistent with a maturation arrest and lack of granulocytic differentiation.

Adolescent↗

PubMed2005

Nano-encapsulation of protein using an enteric polymer as carrier.

In this preliminary work, an enteric polymer has been used for encapsulating bovine serum albumine (BSA) as a model protein drug. Poly (lactide-co- glycolide) has been commonly used for oral administration purposes as a polymer matrix, but in this case an enteric polymer was used effectively to protect the protein in a gastric environment. A modified water/oil/water technique was used to decrease the particle diameter, and transmission electron microscopy experiments showed that the average diameter of the nanoparticles obtained was below 100 nm. The spherical nature of the particles and their diameters strongly depend on the control of the process parameters. The encapsulation efficiency was 77% for sample B4, and protein release profiles for both samples B3 and B4 indicate that these systems possess controlled-release characteristics. Finally, as a result of electrophoresis (SDS-PAGE), the BSA was not chemically affected under encapsulation conditions.

Animals↗

PubMed2005

Biological modifiers as cytoreductive therapy before stem cell transplant in previously untreated patients with multiple myeloma.

BACKGROUND: High dose chemotherapy with supporting autologous stem cell transplantation is now considered the treatment of choice in patients with multiple myeloma <65 years old. The best regimen appears to be VAD (vincristine, doxorubicin and dexamethasone), but acute and late toxicity can limit the use of this combination. The use of biological modifiers has not been considered in this situation. We developed a new cytoreductive regimen, in an attempt to retain clinical efficacy but reduce toxicity. PATIENTS AND METHODS: Thirty-six patients, previously untreated with diagnosis of multiple myeloma were enrolled to received the DAI regimen (dexamethasone 30 mg/m(2), i.v., days 1-4, all-trans-retinoic acid 45 mg/m(2), p.o., days 5-14 and interferon alpha 2a, 4.5 MU s.c., days 5-14) administered every 28 days for six cycles before high-dose chemotherapy (melphalan 200 g/m(2)) and autologous stem cell transplantation. RESULTS: Overall response was observed in 29 cases (80%), complete response in 19 and partial response in 10 patients. Five patients were >65 years old and were treated with dexamethasone/thalidomide. Twenty-four patients underwent transplants. At a median follow-up of 31.6 months, no relapse or disease progression was observed, thus actuarial curves at 3-years showed that event-free survival was 86% and overall survival was 94%. Toxicity was mild. CONCLUSIONS: This regimen appears to be an excellent alternative as cytoreductive treatment before high-dose chemotherapy and autologous stem cell transplantation with excellent overall response and minimal toxicity. Controlled clinical trials are warranted to define the role of this new therapeutic approach.

Administration, Oral↗

PubMed2005

[Effectiveness of the implementation of a clinical program (CP) for the management of acute pharyngitis in adults].

OBJECTIVE: To reduce variability in the diagnosis and treatment of acute pharyngitis, reaching an established standard of quality. DESIGN: Noncontrolled intervention study, consisting of sequential quality improvement cycles. SETTING: Unscheduled attention at the outpatient clinic of an internal medicine service. PARTICIPANTS: a baseline sample and 7 bimonthly follow-up samples were randomly selected from 2764 visits for acute pharyngitis and tonsillitis, resulting in a total sample of 910 visits. We include patients of both sexes who were at least 15 years old. A staff of 19 physicians are in charge of the outpatient clinic. Seventy five visits (8.2%) were eliminated because of lack of data. INTERVENTIONS (CLINICAL PROGRAM): a) elaboration of the CP; b) information to the physicians; c) monitoring of the indicators every two months; and d) introduction of corrective measures after the basal measurement and after each monitoring, including the communication to the professionals of the global and individual results. MAIN MEASUREMENTS: The following indicators were obtained from the computerized medical record: use of rapid antigen test for streptococcus (URAT), total antibiotic prescription (TAP), suitable antibiotic use (SAU) and first choice antibiotic selection (FCAS). The respective standards were adapted from international guidelines with the consensus of the intervening professionals, namely: URAT 50%; TAP 20%; SAU 100% and FCAS 100%. STATISTICAL ANALYSIS: the indicators temporal variations were analyzed according the chi square test for linear trend. RESULTS: the URAT increased significantly from the basal 30% and reached the 50% standard (P=.01). The basal TAP was 36% and it did not change significantly with the intervention (P=.53). The SAU improved significantly from basal 34% to values between 60 and 80% (P<.0001), about half of the maximal attainable improvement. The FCAS was 18% in the basal sample and climbed to 75% in the last measurements (P<.0001), about two thirds of the maximal attainable improvement. CONCLUSIONS: Although the physicians' attitude has changed, it is still a long way from the established standard. It is necessary to maintain the monitoring of the quality indicators and the regular and customized interventions until the consolidation of the practice is achieved.

Acute Disease↗