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Biomedical subjects

C Rodriguez

Publications and source records attributed to C Rodriguez.

At least 145 records · Page 8Linked to original sources

Effect of apolipoprotein E and A-IV phenotypes on the low density lipoprotein response to HMG CoA reductase inhibitor therapy.

Our purpose was to assess the effect of apolipoprotein (apo) E and apo A-IV isoform variation on low density lipoprotein (LDL) cholesterol lowering response to the HMG CoA reductase inhibitor, pravastatin. Plasma samples were obtained from participants (apo E, n = 97; apo A-IV, n = 144) in the PLAC-I (Pravastatin Limitation of Atherosclerosis in Coronary Arteries Study-1). The mean LDL cholesterol reduction in these subjects who were randomized to pravastatin 40 mg/day was 28%. Subjects with the APOE*2 allele (n = 12) had significantly (P = 0.04) greater reductions at 36% than subjects homozygous for the APOE*3 allele (n = 66, 27%) or those with the APOE*4 allele (n = 19, 26%). No significant effect of apo A-IV phenotype on LDL cholesterol lowering in response to pravastatin was noted. A meta-analysis utilizing published data from 4 previously published studies as well as our own data with a total sample size of 625 subjects was carried out. This analysis indicates that the presence of the APOE*2 allele was associated with a significantly greater (P < 0.05) LDL-cholesterol lowering response at 37% than those subjects homozygous for the APOE*3 allele at 35%, while those with the APOE*4 allele had a significantly lower response (P < 0.05), at 33%. These data are consistent with the concept that apo E phenotype modulates the LDL cholesterol lowering response observed with the use of HMG CoA reductase inhibitors.

Alleles↗

Predictive factors of enrollment and adherence in a breast cancer screening program in Barcelona (Spain).

This paper study the predictive factors associated to enrollment and adherence in a breast cancer screening program in Barcelona, Spain; the Program is targeted to women 50-70 years of age who are members of a Health Maintenance Organization. Data were collected by personal interview for the attending women and by telephone in the non-attending group. The questionnaire was focused on knowledge, attitudes and practices related to female cancer prevention and breast cancer risk factors. Data analysis consisted of bivariate and multivariate analysis. Enrolling in a breast cancer screening program was strongly associated with practices related to cancer prevention in the bivariate analysis. Having had a previous mammography was the only behavioral factor that showed an independent relationship with enrollment (OR = 6.45, 95% CI = 3.35-12.42) in the multivariate analysis together with being younger than 55 and having family history of cancer. Adherence was associated with having the best opinion of the program, knowing the preventive role of mammography and performing regular breast self-examination in the bivariate analysis; of these, knowing the preventive role of mammography (OR = 2.66, 95% CI = 1.14-6.18) and performing regular breast self-examination (OR = 1.99, 95% CI = 1.23-3.23) were independently associated in the multivariated analysis. Being a relative of a municipal worker and younger than 55 were also significantly associated with adherence. Getting women to participate in a breast cancer screening program is difficult--mailed invitation letters are not sufficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

B cells capable of spontaneous IgG secretion in cerebrospinal fluid from patients with multiple sclerosis: dependency on local IL-6 production.

Cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients contains B cells capable of spontaneous IgG secretion in vitro. This study analyses the function and regulation of these cells. CSF cells obtained from nine MS patients actively produced IgG during 2-3 days in culture, and the activity decreased when CSF cells were cultured in serum-free medium. CSF cells from four controls did not secrete detectable IgG in vitro. Further experiments revealed that IL-6 played a role on MS CSF IgG-secreting cells, as can be deduced from the following findings: (i) the addition of exogenous IL-6, but not of other cytokines, to serum-free cultures restored missing CSF cell IgG secretion (ii) the inclusion of anti-IL-6, but not of control, blocking MoAb reduced IgG secretion by CSF cells in fetal calf serum (FCS)-containing cultures; and (iii) CSF cells were capable of active IL-6 production in the presence of FCS. These results suggest that endogenous IL-6 production by MS CSF cells seems to be responsible for inducing CSF IgG-secreting B cells to reach terminal differentiation.

Adult↗

Comparison of the kinetics of sodium meclofenamate versus meclofenamic acid after oral administration to sheep.

Meclofenamates are non-steroidal anti-inflammatory agents used in ruminants for the prevention and the treatment of anaphylactic processes. The objective of the present work was to study possible kinetic variations due to the chemical form of meclofenamates administered by the oral route to adult sheep. Six Rubia del Molar female sheep (2-3 years old, 47-57 kg) were used. Initially, an intravenous administration of sodium meclofenamate (2.2 mg/kg bwt) was given; the obtained kinetic results were in agreement with data from other authors. Oral administrations (20 mg/kg bwt) of sodium meclofenamate and meclofenamic acid were then given. When the reticular groove was opened, both drug forms showed a single meclofenamate plasma peak; t2max were 60.0 +/- 10.61 min and 127.50 +/- 22.5 min for the sodium and acid form, respectively. The elimination rate constants (beta) were not significantly different, but the absorption half-lives were (14.69 +/- 3.21 min for the sodium form and 61.07 +/- 21.7 min for the acid form). The bioavailability was 48.6 +/- 4.3% for sodium meclofenamate and 65.1 +/- 2.8% for meclofenamic acid. Thus, the chemical form (sodium versus acid) alters the oral bioavailability and tmax of meclofenamates in adult sheep. These findings agree with the behaviour of meclofenamates in man.

Administration, Oral↗

The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes.

Recently, melatonin was found to be the most potent physiological free radical scavenger known to date. In this work, we attempted to define the role this neurohormone plays in the regulation of apoptosis, since the effect of bcl-2, the main gene implicated in its inhibition, acts via an antioxidant mechanism. We investigated the role of melatonin in cell death of thymus, a well known model for the study of apoptosis. Two sets of experiments were carried out: in vivo experiments, performed with Wistar rats, and in vitro experiments, performed with primary cultures of young Wistar rat thymocytes treated with glucocorticoids in order to induce apoptosis. Morphometrical studies in semithin sections of thymus and analysis of DNA fragmentation by gel electrophoresis show that physiological apoptosis occurring in thymus of 65 days old rats, is prevented by the daily administration of melatonin beginning when the rats were 25 days old. Also, we found that at a concentration of 10(-7) M, melatonin decreases by 35% the percentage of apoptotic cells induced by glucocorticoids in cultured thymocytes of 25 day old rats. 10(-9) M melatonin decreases cell death by 20%. Finally, melatonin at 10(-11) M did not have any effect. Several hypothesis are discussed to explain this effect: direct interaction of melatonin with glucocorticoid receptors in the thymus; induction of interleukin-4 release; direct genomic action modulating the expression of apoptosis-inhibiting genes; an effect on nitric oxide synthase; and finally, the antioxidant action of melatonin. Since apoptosis is a possible mechanism involved in neuronal death shown in several neurodegenerative diseases such as Parkinson or Alzheimer's diseases, investigative efforts should be directed to the possible role of melatonin in inhibiting cell death in tissues other that the thymus. Melatonin might be a potent therapeutic agent in some of these conditions.

Aging↗

Human gp130 transducer chain gene (IL6ST) is localized to chromosome band 5q11 and possesses a pseudogene on chromosome band 17p11.

Human gp130 (IL6ST) is one of the most widely used chains of the cytokine receptor family. Indeed, it is involved in signal transduction of interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor. In a previous report, IL6ST was assigned to chromosomes 5 and 17. Here we specify the chromosomal sublocalization of IL6ST and show that the sequence detected on 17p11 corresponds, in fact, to a nontranscribed pseudogene, whereas the active gene is located at chromosome band 5q11.

Antigens, CD↗

The lethal effects of cytokine-induced nitric oxide on cardiac myocytes are blocked by nitric oxide synthase antagonism or transforming growth factor beta.

Inducible nitric oxide (NO) produced by macrophages is cytotoxic to invading organisms and has an important role in host defense. Recent studies have demonstrated inducible NO production within the heart, and that cytokine-induced NO mediates alterations in cardiac contractility, but the cytotoxic potential of nitric oxide with respect to the heart has not been defined. To evaluate the role of inducible nitric oxide synthase (iNOS) on cardiac myocyte cytotoxicity, we exposed adult rat cardiac myocytes to either cytokines alone or to activated J774 macrophages in coculture. Increased expression of both iNOS message and protein was seen in J774 macrophages treated with IFN gamma and LPS and cardiac myocytes treated with TNF-alpha, IL-1 beta, and IFN gamma. Increased NO synthesis was confirmed in both the coculture and isolated myocyte preparations by increased nitrite production. Increased NO synthesis was associated with a parallel increase in myocyte death as measured by CPK release into the culture medium as well as by loss of membrane integrity, visualized by trypan blue staining. Addition of the competitive NO synthase inhibitor L-NMMA to the culture medium prevented both the increased nitrite production and the cytotoxicity observed after cytokine treatment in both the isolated myocyte and the coculture experiments. Because transforming growth-factor beta modulates iNOS expression in other cell types, we evaluated its effects on cardiac myocyte iNOS expression and NO-mediated myocyte cytotoxicity. TGF-beta reduced expression of cardiac myocyte iNOS message and protein, reduced nitrite production, and reduced NO-mediated cytotoxicity in parallel. Taken together, these experiments show the cytotoxic potential of endogenous NO production within the heart, and suggest a role for TGF-beta or NO synthase antagonists to mute these lethal effects. These findings may help explain the cardiac response to sepsis or allograft rejection, as well as the progression of dilated cardiomyopathies of diverse etiologies.

Amino Acid Oxidoreductases↗

Etiology and therapy of chronic suppurative otitis.

Infectious diseases of the ear are important in adults due to their incidence and relapses. We carried out a study of aerobic microorganisms on 251 otic exudates from patients diagnosed as having chronic suppurative otitis media without cholesteatoma (119), chronic suppurative otitis media with cholesteatoma (85) and chronic external otitis (47). The microorganisms predominantly isolated were, Pseudomonas aeruginosa, Staphylococcus aureus and other Enterobacteriaceae. 86% of isolates were monomicrobial and 14% of isolates were polymicrobial. In these latter the predominantly isolated microorganisms were also P. aeruginosa, S. aureus, Corynebacterium spp. and Proteus mirabilis. P. aeruginosa was the most commonly isolated and showed the highest percentages of resistance against antimicrobial agents tested. P. aeruginosa was most susceptible to ciprofloxacin and imipenem, but much less susceptible to cefotaxime, moxalactam and trimethoprim-sulfamethoxazole. S. aureus was highly sensitive to amoxicillin/clavulanate, trimethoprim-sulfamethoxazole, rifampin and teichoplanin. 100% of the isolates were resistant to penicillin G and ampicillin.

Adolescent↗

Gene expression, polarising activity and skeletal patterning in reaggregated hind limb mesenchyme.

The developing chick limb has two major signalling centres; the apical ectodermal ridge maintains expression of several important genes and outgrowth of the limb, and the polarising region specifies the pattern of skeletal elements along the anteroposterior axis. We have used reaggregated leg grafts (mesenchyme dissociated into single cells, placed in an ectodermal jacket and grafted to a host) to study patterning in a system where the developmental axes are severely disrupted. Reaggregates from different regions of leg mesenchyme developed correspondingly different digits, giving a system in which skeletal phenotype could be compared with the expression of genes thought to be important in patterning. We found that posterior third and whole leg reaggregates gave rise to different digits, yet expressed the same combination of HoxD, Bmp-2 and shh genes throughout their development. Anterior thirds initially only express the 3' end of the HoxD cluster but activate the more 5' members of the cluster sequentially over a period of 48 hours, a period during which Bmp-2 is activated but no shh or Fgf-4 expression could be detected. Our results suggest that there are two independent mechanisms for activating the HoxD complex, one polarising region-dependent and one independent, and that shh expression may not be necessary to maintain outgrowth and patterning once a ridge has been established.

Animals↗

Comparison of derivatization procedures for the determination of diuretics in urine by gas chromatography-mass spectrometry.

Three different GC-MS screening procedures, which use different ways of derivatization (methylation), are compared. In the first one, derivatization with iodomethane in acetone and a previous solid-liquid extraction is used; the second one is based on an extractive alkylation method using iodomethane in toluene (liquid-liquid extraction); and the last one is flash methylation by pyrolysis of tetraalkylammonium salts in the injector of the gas chromatograph using trimethylanilinium as the derivatization agent. The speed of the extraction, reproducibility and accuracy have been compared for 20 diuretics including the ones most often used in sports, such as bumetanide, ethacrynic acid, acetazolamide, dichlorphenamide, furosemide, hydroflumethiazide, hydrochlorothiazide and chlorthalidone; they have also been applied to the two uricosuric agents probenecid and benzbromarone.

Diuretics↗

Effect of fat feeding on human intestinal apolipoprotein B mRNA levels and editing.

Our purpose was to assess the effect of a fat-rich meal on intestinal apolipoprotein B (apoB) mRNA levels and editing. We obtained jejunal biopsies from eight healthy adults in the fasting state and 3 h after a meal containing 1 g/kg of fat. In the fasting state, 93% of the apoB mRNA contained the editing sequence resulting in apoB-48 production. Feeding induced no significant changes in apoB mRNA levels or editing. Our data are consistent with the concept that the significant increase in apoB-48 within triglyceride-rich lipoproteins in postprandial plasma is not due to alterations in apoB gene expression or editing.

Apolipoproteins B↗

Molecular analysis of the IL-6 receptor in human multiple myeloma, an IL-6-related disease.

A PCR-SSCP approach was used to search for mutations in IL-6 receptor genes in 9 human plasma cell lines (HMCL) and in tumor plasma cells from 19 patients with fulminating multiple myeloma, an IL-6-related disease. Whereas no mutation was found in the cytokine receptor homologous (CRH) domain of IL-6R alpha, DNA and RNA polymorphisms in the gp130 CRH domain was detected in tumoral samples as well as in blood samples from healthy donors. Finally, mutations in the gp130 critical cytoplasmic domain were found in one HMCL and in tumor plasma cells of one patient. Only the mutated allele was expressed in the HMCL.

Antigens, CD↗

Genetic structure is determined by stochastic factors in a natural population of Drosophila buzzatii in Argentina.

D. buzzatii is a cactophilic species associated with several cactaceae in Argentina. This particular ecological niche implies that this species is faced with a non-uniform environment constituted by discrete and ephemeral breeding sites, which are colonized by a finite number of inseminated females. The genetic consequences of this population structure upon the second chromosome polymorphism were investigated by means of F-statistics in a natural endemic population of Argentina. The present study suggests that differentiation of inversion frequencies in third instar larvae among breeding sites has taken place mainly at random and selection is not operating to determine the structure of this population. The average number of parents breeding on a single pad seems to be similar to the number colonizing Opuntia ficus indica rotting cladodes in Carboneras, a derived population from Spain. There is no significant excess of heterokaryotypes within pads or in the population as a whole. The results obtained in the present study suggest that the potential role of selective versus stochastic factors relative to the among pad heterogeneity in the population here studied is different from that of the Spanish population previously reported. Potential mechanisms responsible for these differences are discussed.

Animals↗

Effects of softened and unsoftened fabrics on infant skin.

BACKGROUND: The effects of softened and unsoftened fabrics on the skin of infants of 1-12 months of age were evaluated under real life conditions of skin contact with fabrics. METHODS: During 4 weeks, 24 infants wore cotton fabrics washed with a granular detergent on one side of their lower back, and on the other side, cotton fabrics washed with the same detergent and softened with a liquid fabric softener. Skin effects were evaluated by visual grading for redness, dryness, and smoothness, by skin stripping and measuring of Chroma C* (squamometry), by measurements of elasticity and bioelastic ratio, and by instrumental measurements of skin parameters (pH, capacitance, transepidermal water loss (TEWL), and erythema by colorimetry). RESULTS: No deleterious effects were observed in any infant. A decrease in squamometry (Chroma C*) and an increase in capacitance were detected in skin exposed to softened fabrics relative to unsoftened ones. Values of pH tended to be higher in the sites treated with softened versus unsoftened fabrics (pH 6.06 and 5.87, respectively, at end of study). All other parameters showed no significant differences in the two treatment groups. CONCLUSIONS: Neither softened nor unsoftened fabrics produced any adverse effects on the skin of infants after continuous wearing during 29 days. A slight beneficial effect on the infants' skin was observed with softened relative to unsoftened fabrics. Methods measuring the structure and function of the stratum corneum were more sensitive discriminators of the effects of fabrics on the skin than traditional methods of visual clinical evaluation.

Double-Blind Method↗