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Biomedical subjects

M Aranda

Publications and source records attributed to M Aranda.

At least 19 recordsLinked to original sources
PubMed2003

Dose dependence of the growth rate of multicellular tumour spheroids after irradiation.

The present study investigated differences in the growth rate of multicellular tumour spheroids of the MCF-7 line of human breast cancer before and after their irradiation. Growth of the spheroids was analysed according to a model based on a Gompertz function. In this model, normalization to a common initial volume is achieved in a way that enables meaningful comparisons to be made between the results obtained for each spheroid. For irradiated spheroids the model includes an additional term to take account of sterilized cells. We found that the growth rate observed before irradiation is not fully recovered by irradiated spheroids and that growth recovery reduces with higher irradiation doses. Surviving fractions obtained at doses below 3 Gy are comparable with those found in clonogenic assays on spheroids of the same cellular line. At larger doses, discrepancies between the different studies are considerable.

Breast Neoplasms↗
PubMed2001

Altered directionality in the Cre-LoxP site-specific recombination pathway.

The site-specific recombinase Cre must employ control mechanisms to impose directionality on recombination. When two recombination sites (locus of crossing over in phage P1, loxP) are placed as direct repeats on the same DNA molecule, collision between loxP-bound Cre dimers leads to excision of intervening DNA. If two sites are placed as inverted repeats, the intervening segment is flipped around. Cre catalyzes these reactions in the absence of protein co-factors. Current models suggest that directionality is controlled at two steps in the recombination pathway: the juxtaposition of loxP sites and the single-strand-transfer reactions within the synaptic complex. Here, we show that in Escherichia coli strain 294-Cre, directionality for recombination is altered when the expression of Cre is increased. This leads to deletion instead of inversion on substrates carrying two loxP sites as inverted repeats. The nucleotide sequence composition of loxP sites remaining in aberrant products indicates that site alignment and/or DNA strand transfer in the in vivo Cre-loxP recombination pathway are not always tightly controlled.

Attachment Sites, Microbiological↗
PubMed2000

Comparison of twice-daily stavudine plus once- or twice-daily didanosine and nevirapine in early stages of HIV infection: the scan study.

OBJECTIVES: To evaluate the safety and effectiveness of once-daily didanosine and nevirapine plus twice-daily stavudine versus twice-daily administration of all three drugs. METHODS: This open-label, randomized, multicentre study enrolled 94 antiretroviral-naive patients with chronic HIV infection, CD4+ cell counts > 500 x 10(6) cells/l, and viral loads > 5000 copies/ml. Patients were treated with either 40 mg stavudine (twice daily) plus 400 mg didanosine (once daily) and 400 mg nevirapine (once daily) or 40 mg stavudine (twice daily) plus 200 mg didanosine (twice daily) and 200 mg nevirapine (twice daily). RESULTS: After 12 months, 68% of patients who received twice-daily didanosine and nevirapine had viral loads < 200 copies/ml in the intention-to-treat and 79% in the on-treatment analysis, respectively. The corresponding values for patients treated with didanosine and nevirapine, taken once-daily, were 73 and 85%. The percentages of patients in each group with viral loads < 5 copies/ml at 12 months were 40% (once daily ) and 45% (twice daily) for the intention-to-treat analysis. Five of 11 patients (45%) with plasma viral loads < 5 copies/ml at 12 months had detectable virus in tonsillar tissue. Genotypic resistance to nevirapine was noted in seven of the 14 patients with detectable viral load at month 12. Mean changes in CD4+ cell counts for patients treated with stavudine plus once- or twice-daily didanosine and nevirapine were 154 and 132 x 10(6) cells/l, respectively. Treatment was interrupted due to adverse events in seven patients (8%) (four who received once-daily didanosine and nevirapine and three treated with twice-daily doses). CONCLUSIONS: The combination of twice-daily stavudine plus once-daily didanosine and nevirapine was as safe and well tolerated as twice-daily administration of all three agents. Both regimens were equally effective in reducing viral loads and in increasing CD4+ cell counts.

Anti-HIV Agents↗
PubMed2000

Detection and localization of pulmonary air leaks using laser-polarized (3)He MRI.

Pulmonary air leaks were created in the lungs of Yorkshire pigs. Dynamic, 3D MRI of laser-polarized (3)He gas was then performed using a gradient-echo pulse sequence. Coronal magnitude images of the helium distribution were acquired during gas inhalation with a voxel resolution of approximately 1.2 x 2.5 x 8 mm, and a time resolution of 5 sec. In each animal, the ventilation images reveal focal high-signal intensity within the pleural cavity at the site of the air leaks. In addition, a wedge-shaped region of increased parenchymal signal intensity was observed adjacent to the site of the air leak in one animal. (3)He MRI may prove helpful in the management of patients with pulmonary air leaks.

Administration, Inhalation↗
PubMed2000

Anesthetics, sedatives, and paralytics. Understanding their use in the intensive care unit.

This article reviews the use of inhalational, intravenous, and epidural agents used in the operating room and ICU. An emphasis is placed on the rationale for their selection. Additionally, the side effects and expected complications are discussed. By developing expertise with one's own repertoire of sedatives, narcotics, and neuromuscular blocking agents, one may decrease postoperative complications and lengths of stay.

Anesthesia, Epidural↗
PubMed2000

Inhaled nitric oxide and pulmonary vasoreactivity.

Inhaled nitric oxide is a ubiquitous molecule which is produced endogenously and is also found in air pollution and in cigarette smoke. After describing the chemistry of NO, we review its history from the first description in 1980 to the current clinical indications. The biosynthesis of NO, its effects on pulmonary vasoreactivity, and the administration of inhaled NO will be described. The indications, uses, and side effects of inhaled NO are discussed with an emphasis on withdrawal of NO therapy, specifically the "rebound" phenomenon. Possible drug interactions are listed. Inhaled nitric oxide is here to stay, and future studies will provide more information on its therapeutic dose, duration and potential toxicity.

Administration, Inhalation↗
PubMed2000

Assessment of in vitro mutagenicity in Salmonella and in vivo genotoxicity in mice of the mycotoxin fumonisin B(1).

Fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium moniliforme, is a contaminant of cereals with various and complex cellular effects. FB(1) induces liver cancer in rats and has been linked to esophageal cancer in South Africa and China. The mechanisms of FB(1)-induced carcinogenesis are uncertain and the information on FB(1) mutagenic properties is limited and controversial. FB(1) contamination levels in maize and wheat from Chile were found to be similar to those in other countries. FB(1) was devoid of activity in gene mutation assays with Salmonella typhimurium strains TA100, TA102 and TA98. However, i.p. injection of FB(1) induced an increased frequency of micronuclei in mouse bone marrow polychromatic erythrocytes at 25 and 100 mg/kg. We conclude that FB(1) induces in vivo genotoxicity in the absence of in vitro mutagenicity in Salmonella.

Animals↗
PubMed1999

Combined therapy with inhaled nitric oxide and intravenous vasodilators during acute and chronic experimental pulmonary hypertension.

UNLABELLED: Both inhaled nitric oxide (NO) and IV vasodilators decrease pulmonary hypertension, but the effects of combination therapy are unknown. We studied the response to inhaled NO (100 ppm) alone, IV vasodilator alone, and combined therapy during acute (U46619-induced) and chronic (monocrotaline-induced) pulmonary hypertension in the pentobarbital-anesthetized rat. Vasodilator doses were 1.0, 3.2, 10, and 32 microg x kg(-1) x min(-1) sodium nitroprusside (SNP); 50, 100, 150, 200, and 300 microg x kg(-1) x min(-1) adenosine; or 25, 50, 150, 200, and 300 ng x kg(-1) x min(-1) prostacyclin. In the absence of IV vasodilator therapy, inhaled NO decreased mean pulmonary artery pressure without decreasing mean systemic arterial pressure. In both acute and chronic pulmonary hypertension, the addition of inhaled NO to the largest dose of adenosine or prostacyclin, but not of SNP, decreased pulmonary artery pressure. Because inhaled NO and SNP activate guanylyl cyclase and adenosine and prostacyclin activate adenylyl cyclase, the results suggest that adding inhaled NO to a vasodilator not dependent on guanylyl cyclase may produce additional selective pulmonary vasodilation. IMPLICATIONS: In therapy of pulmonary hypertension, inhaled nitric oxide should produce additional selective pulmonary vasodilation when combined with a vasodilator whose mechanism of action is not dependent on cyclic guanosine 3',5'-monophosphate.

Acute Disease↗
PubMed1999

Rabies in skunks from Mexico.

An enzootic focus of rabies in skunks in Mexico is described. Fifty three wild animals including two badgers (Taxidea taxus), 32 bats (various species), one bobcat (Lynx rufus), two coatis (Nasua narica) three foxes (Urocyon cineroargenteus), one raccoon (Procyon lotor) and 12 skunks (see below) were tested for rabies by direct immunofluorescence assay from 1991 to 1997 in the central part of San Luis Potosi State, Mexico. Rabies occurrence was 21% of all tested mammals, with 19% in skunks and only 2% in other wild species (one bobcat). Skunks represented 23% of all mammals tested and had a rabies prevalence of 83%. Only 10 individuals were identified: three hog-nosed skunks (Conepatus leuconotus) and seven spotted skunks (Spilogale putorius). All were involved in human attacks; the spotted skunk attacks were inside bedrooms while people were sleeping, and the hog-nosed skunk attacks occurred outdoors. Skunk cases of rabies represented 40% of all rabies cases in 1997, and 100% of cases registered for wild animals in San Luis Potosi state. This situation constitutes an important public health problem and requires further epidemiological research to make the human population aware of the problem and to establish measures to limit further human attacks by rabid skunks.

Animals↗
PubMed1999

Methyl bromide decreases excitability without having immediate toxic effects in rat hippocampal CA1 neurons in vitro.

Methyl bromide, a disinfectant gas amply used worldwide, is neurotoxic in humans and other mammals. To study its short-term effects on neurons, it was applied in aqueous solution to hippocampal slices of young rats (1.4 and 0.7 mM; for 8 minutes). Extracellular field recordings and intracellular microelectrode recordings from CA1 pyramidal neurons showed that the neurons stay viable for at least one hour after application of the mono-halomethane. However, a moderate, but consistent, irreversible decrease in synaptic excitability was observed. The intracellular recordings indicate that this may be attributed to a decrease in excitatory postsynaptic potentials. No effects were observed at 0.7 mM methyl bromide. Bromide, in a dose-dependent, partly reversible manner (during one hour), produced a similar decrease in excitability. Quantitatively, the action of bromide at 0.5 mM resembled the one seen with methyl bromide at the concentration of 1.4 mM. Since methyl bromide did not induce electrophysiologic changes consistent with evidence of neurotoxicity during one hour of observation it is concluded that it lacks immediate toxic effects on hippocampal rat neurons. Its neurotoxicity may be entirely due to metabolites or other indirect effects. The slight decrease in excitability may be due to the effect of bromide that is set free as tissue proteins and other cell molecules are methylated.

Animals↗
PubMed1998

Diagnostic utility of postmortem fine-needle aspiration cultures.

BACKGROUND: Microbiological cultures at autopsy have not proved to be very useful. In life, transthoracic and fine-needle aspirations of other tissues have provided better results. The aim of this prospective study was to assess the diagnostic utility of postmortem cultures obtained by fine-needle aspiration puncture (FNAP) of several tissues when punctures were performed in the immediate postmortem period. METHODS: Comparative analysis was performed between FNAP cultures and those obtained in life and by conventional autopsy. All adult autopsied patients who died at a general teaching hospital in a 3-year period were included. Clinical data, microbiological cultures before death, and pathologic data from autopsies of all patients were recorded, as were results of FNAP performed after death from the heart, right lower lung, liver, spleen, and other areas suspicious for infection. Cultures from the same sites were made at autopsy. Microorganisms were isolated and defined as infectious agents, colonizers, or contaminants according to standard criteria. RESULTS: Ninety-two patients (59 men, 33 women) were included in the study; patients had a mean age of 67.7 years. There were five main diagnostic groups: neoplastic (n = 25), digestive (n = 15), respiratory (n = 14), circulatory (n = 10), and infectious diseases (n = 10). Infection was suspected in 47 patients (51.3%). Autopsy was performed 12 hours after death or later in 61% of patients. No significant differences were found in terms of contamination or colonization in relation to time between death and FNAP, time between death and autopsy, or microorganisms isolated. The sensitivity of FNAP and autopsy with respect to the isolation of infective microorganisms was similar (80.9% vs 87%), but FNAP was more specific (66.7% vs 44.4%). Age, sex, time between death and FNAP, clinical diagnosis, cause of death, and antimicrobial therapy did not influence the results significantly. Blood cultures gave the best results (specificity 84.4%) [corrected]. CONCLUSIONS: Fine-needle aspiration puncture performed in the immediate postmortem period adds relevant microbiological information to the clinicopathologic picture and provides higher specificity than autopsy cultures. Blood cultures are especially useful. When difficulties are associated with autopsy examination or in cases of selected clinical conditions, FNAP can be an effective tool for the postmortem diagnosis of infection.

Aged↗
PubMed1998

[Mutations of the p53 suppressor gene in gastric adenocarcinoma].

BACKGROUND: We have shown numeric alterations such as hyperploidy and hypoploidy with loss of chromosome 17 in primary gastric cancer. This chromosome maps p53 suppressor gene that induces the transcription of genes related to cellular cycle control, DNA synthesis and repair, cellular differentiation and apoptosis. AIM: To analyze, at a molecular level, the possible alterations of p53 suppressor gene in samples of gastric cancer and non tumoral mucosa. MATERIAL AND METHODS: Tissue samples of gastric carcinoma and non tumoral gastric mucosa coming from 26 patients subjected to a total gastrectomy were analyzed. The mutation of p53 suppressor gene exons 7 to 9 were determined using a conformational polymorphism analysis in single strands of the gene and indirect sequencing in some cases. RESULTS: Alterations in p53 gene were found in 77% of tumoral and 19% of non tumoral samples. T insertions in codons 260, 317 and 321, G insertion in codon 328 and G-T transvertion in codon 302 were found. Aminoacid sequence analysis of p53 protein obtained with sequencing data showed that T insertion in codon 260 could translate three erroneous aminoacids after the mutation and produce a truncated protein due to the creation of a stop codon. No associations between alterations of p53 gene and clinical or pathological variables such as age, sex, tumor localization, histological type and presence of lymph node metastases were observed. CONCLUSIONS: Mutations of p53 suppressor gene are frequent in gastric carcinoma.

Adenocarcinoma↗