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Biomedical subjects

S Sierra

Publications and source records attributed to S Sierra.

12 recordsLinked to original sources

Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis.

BACKGROUND AND AIMS: Previous studies have described the intestinal anti-inflammatory effects exerted by the bioflavonoid quercitrin (QR) and by an n-3 polyunsaturated fatty acids (PUFA)-enriched diet in experimental models of rat colitis. The aim of the present study was to test if the combination of both treatments would result in an improvement in the intestinal anti-inflammatory effect achieved separately. METHODS: Colitis was induced in female Wistar rats by incorporating dextran sodium sulfate (DSS) in drinking water at 5% (w/v) for 5 days and at 2% (w/v) for the following 10 days. Five groups of rats (n=10) were used: two of them received an olive-oil-based diet with fish oil, rich in n-3 PUFA (FO diet) for 2 weeks before colitis induction and until the end of the experiment, and one of those also was administered daily QR (1mg/kg, PO), starting when DSS concentration was changed. DSS colitis was induced in other two groups fed with standard rat diet, one of them being administered QR as before. A non-colitic group fed standard diet was also included. After that period, the rats were sacrificed and colonic damage was assessed both histologically and biochemically. RESULTS: The concurrent administration of FO diet and QR exhibited an intestinal anti-inflammatory effect, as evidenced by a significant improvement of all biochemical parameters of colonic inflammation assayed in comparison with non-treated colitic rats. Thus, both colonic myeloperoxidase (MPO) and alkaline phosphatase (AP) activities were significantly reduced compared with untreated colitic rats. In addition, a complete restoration of colonic glutathione content, which was depleted as a consequence of the colonic insult, was obtained in rats treated with QR plus FO diet; this content was even higher than that obtained when colitic rats were treated with FO diet alone. When compared with the control colitic group, the combined treatment was also associated with a lower colonic nitric oxide synthase and cyclooxygenase-2 expression as well as with a significant reduction in different colonic proinflammatory mediators assayed, i.e. leukotriene B(4), tumor necrosis factor alpha and interleukin 1beta, showing a significantly greater inhibitory effect of the latter in comparison with rats receiving FO diet without the flavonoid. CONCLUSIONS: These results support the potential synergism between the administration of the flavonoid and the incorporation of olive oil and n-3 PUFA to the diet for the treatment of these intestinal inflammatory disorders.

Alkaline Phosphatase↗

Foot-and-mouth disease virus evolution: exploring pathways towards virus extinction.

Foot-and-mouth disease virus (FMDV) is genetically and phenotypically variable. As a typical RNA virus, FMDV follows a quasispecies dynamics, with the many biological implications of such a dynamics. Mutant spectra provide a reservoir of FMDV variants, and minority subpopulations may become dominant in response to environmental demands or as a result of statistical fluctuations in population size. Accumulation of mutations in the FMDV genome occurs upon subjecting viral populations to repeated bottleneck events and upon viral replication in the presence of mutagenic base or nucleoside analogs. During serial bottleneck passages, FMDV survive during extended rounds of replication maintaining low average relative fitness, despite linear accumulation of mutations in the consensus genomic sequence. The critical event is the occurrence of a low frequency of compensatory mutations. In contrast, upon replication in the presence of mutagens, the complexity of mutant spectra increases, apparently no compensatory mutations can express their fitness-enhancing potential, and the virus can cross an error threshold for maintenance of genetic information, resulting in virus extinction. Low relative fitness and low viral load favor FMDV extinction in cell culture. The comparison of the molecular basis of resistance to extinction upon bottleneck passage and extinction by enhanced mutagenesis is providing new insights in the understanding of quasispecies dynamics. Such a comparison is contributing to the development of new antiviral strategies based on the transition of viral replication into error catastrophe.

Biological Evolution↗

Molecular indetermination in the transition to error catastrophe: systematic elimination of lymphocytic choriomeningitis virus through mutagenesis does not correlate linearly with large increases in mutant spectrum complexity.

Studies with several RNA viruses have shown that enhanced mutagenesis resulted in decreases of infectivity or virus extinction, as predicted from virus entry into error catastrophe. Here we report that lymphocytic choriomeningitis virus, the prototype arenavirus, is extremely susceptible to extinction mutagenesis by the base analog 5-fluorouracil. Virus elimination was preceded by increases in complexity of the mutant spectra of treated populations. However, careful molecular comparison of the mutant spectra of several genomic segments suggests that the largest increases in mutation frequency do not predict virus extinction. Highly mutated viral genomes have escaped detection presumably because lymphocytic choriomeningitis virus replicates at or near the error threshold, and genomes in the transition toward error catastrophe may have an extremely short half-life and escape detection with state-of-the-art cloning and sequencing technologies.

Animals↗

Virus population dynamics, fitness variations and the control of viral disease: an update.

Viral quasispecies dynamics and variations of viral fitness are reviewed in connection with viral disease control. Emphasis is put on resistance of human immunodeficiency virus and some human DNA viruses to antiviral inhibitors. Future trends in multiple target antiviral therapy and new approaches based on virus entry into error catastrophe (extinction mutagenesis) are discussed.

Anti-HIV Agents↗

Efficient virus extinction by combinations of a mutagen and antiviral inhibitors.

The effect of combinations of the mutagenic base analog 5-fluorouracil (FU) and the antiviral inhibitors guanidine hydrochloride (G) and heparin (H) on the infectivity of foot-and-mouth disease virus (FMDV) in cell culture has been investigated. Related FMDV clones differing up to 10(6)-fold in relative fitness in BHK-21 cells have been compared. Systematic extinction of intermediate fitness virus was attained with a combination of FU and G but not with the mutagen or the inhibitor alone. Systematic extinction of high-fitness FMDV required the combination of FU, G, and H. FMDV showing high relative fitness in BHK-21 cells but decreased replicative ability in CHO cells behaved as a low-fitness virus with regard to extinction mutagenesis in CHO cells. This confirms that relative fitness, rather than a specific genomic sequence, determines the FMDV response to enhanced mutagenesis. Mutant spectrum analysis of several genomic regions from a preextinction population showed a statistically significant increase in the number of mutations compared with virus passaged in parallel in the absence of FU and inhibitors. Also, in a preextinction population the types of mutations that can be attributed to the mutagenic action of FU were significantly more frequent than other mutation types. The results suggest that combinations of mutagenic agents and antiviral inhibitors can effectively drive high-fitness virus into extinction.

Animals↗

Response of foot-and-mouth disease virus to increased mutagenesis: influence of viral load and fitness in loss of infectivity.

Passage of foot-and-mouth disease virus (FMDV) in cell culture in the presence of the mutagenic base analog 5-fluorouracil or 5-azacytidine resulted in decreases of infectivity and occasional extinction of the virus. Low viral loads and low viral fitness enhanced the frequency of extinction events; this finding was shown with a number of closely related FMDV clones and populations differing by up to 10(6)-fold in relative fitness in infections involving either single or multiple passages in the absence or presence of the chemical mutagens. The mutagenic treatments resulted in increases of 2- to 6.4-fold in mutation frequency and up to 3-fold in mutant spectrum complexity. The largest increase observed corresponded to the 3D (polymerase)-coding region, which is highly conserved in nonmutagenized FMDV populations. As a result, nucleotide sequence heterogeneity for the 3D-coding region became very similar to that for the variable VP1-coding region in FMDVs multiply passaged in the presence of chemical mutagens. The results suggest that strategies to combine reductions of viral load and viral fitness could be effectively associated with extinction mutagenesis as a potential new antiviral strategy.

Amino Acid Substitution↗

[Quasispecies and molecular evolution of viruses].

Ribonucleic acid (RNA) viruses evolve as complex distributions of genetically different but closely related variants termed viral quasispecies. The precise genome of a quasispecies cannot be defined, since the consensus genome is an average of many variants. The dynamics of quasispecies has considerable implications for the understanding of the adaptability and pathogenic potential of viruses, and in addition, for the design of preventive and therapeutic measures for the diseases caused by these viruses. The authors summarise current knowledge on the structure of quasispecies, and the biological implications of this structure.

Adaptation, Biological↗

Current perspectives on radiation-induced breast cancer.

PURPOSE: An approach to screening and detection of radiation-induced breast cancer is offered. Primary and secondary prevention strategies are suggested and the need for prospective clinical trials is emphasized. METHODS: Data are reviewed from published evidence of radiation-induced breast cancer secondary to atomic bomb radiation, occupational, and therapeutic exposure, especially that incurred during successful treatment of Hodgkin's disease (HD). Preclinical studies are reviewed to explore potential risk factors. RESULTS: Risk factors evident in the link between radiation and breast cancer include the differentiation of breast tissue as mediated by age and hormonal influence. Evidence is presented exploring the link between genetics and breast cancer, including specific genes such as the BRCA1 and BRCA2 genes, the p53 gene, the ataxia telangiectasia (AT) gene, and other nonspecific alterations in DNA repair proficiency. In light of these findings, steps toward primary prevention are discussed, including avoiding radiation exposure, genetic screening, and manipulation of the hormonal milieu. Secondary prevention may also be possible with the use of tamoxifen, low-fat diets, and/or the consumption of flaxseed. CONCLUSION: Our current recommendations for patients irradiated before 30 years of age for Hodgkin's disease include breast self-examination (BSE) monthly, yearly mammography 8 years postirradiation, and regular physical examinations every 6 months. Given the clear link between radiation exposure and breast cancer, we strongly recommend a prospective trial randomize patients to different levels of intensity of surveillance to monitor the efficacy of such screening efforts.

Age Factors↗

The effect of educational brochures on follow-up compliance in women with abnormal Papanicolaou smears.

OBJECTIVE: To determine whether women with abnormal Papanicolaou smears who received educational brochures at the initial booking for colposcopy were more likely to complete recommended treatment and follow-up after 18-24 months than were those who did not receive the brochures. METHODS: One hundred eight women participated in an earlier randomized study of the effect of educational brochures on emotional distress and knowledge about abnormal Papanicolaou smears. Their medical records were reviewed 18-24 months later for completed treatment and follow-up compliance. RESULTS: Women who received the brochure had more completed treatment and follow-up compliance (75.4%) than did those who did not receive the brochure (45.8%). The difference in compliance was 30% (99% confidence interval [CI] 6-54%, P = .002). There were no significant differences in age, education, marital status, or levels of emotional distress between subjects with complete and incomplete follow-up. Knowledge of the recommended number of follow-up visits was greater in women who completed follow-up (difference in frequency 30.4%; 99% CI 7-54%, P = .002). All women with completed treatment and follow-up who had received the brochure found it helpful. CONCLUSIONS: Given the high patient acceptability and demonstrated effectiveness in improving completed treatment and follow-up compliance, educational brochures should routinely accompany, or immediately follow, notification about abnormal Papanicolaou smears.

Adult↗

The effect of educational brochures on knowledge and emotional distress in women with abnormal Papanicolaou smears.

OBJECTIVE: To determine whether an educational brochure about abnormal Papanicolaou smears could reduce psychological distress and concerns about cancer and future health, and increase knowledge about dysplasia and the investigation, treatment, and recommended follow-up. METHODS: One hundred twenty-five consecutive women with dysplasia on a Papanicolaou smear referred to a colposcopy clinic for their first examination were alternately assigned to receive a mailed educational brochure the same day or to receive no brochure. At the colposcopy clinic, consenting women were given the Brief Symptom Inventory, specific questions about feelings regarding an abnormal smear, and a knowledge quiz about dysplasia, colposcopy, and the recommended follow-up. RESULTS: Women who received the brochure were significantly less distressed on the Brief Symptom Inventory and were less anxious about the abnormal Papanicolaou smear, the fear of cancer, and their future health than were women not receiving the brochure. Study women also performed significantly better on knowledge questions about dysplasia, colposcopy, and the recommended follow-up. CONCLUSION: Given the low cost, ease of delivery, and usefulness of educational brochures in reducing psychological distress and increasing knowledge specific to the condition, an educational brochure should routinely accompany or immediately follow notification about an abnormal Papanicolaou smear.

Adult↗

[Il-10 expression is involved in the regulation of the immune response by omega 3 fatty acids].

INTRODUCTION: Polyunsaturated fatty acids play a key role in a huge number of biological functions. Western diets are highly rich in w-6 fatty acids. However the content of w-3 fatty acids is not suitable in those diets, despite of their importance in normal development of the human body and regulation of immune response. The aim of this work is to examine the effect of w-3 fatty acids enriched diet in the regulation of inflammatory response. MATERIAL AND METHODS: Balb/c mice were fed either w-6 fatty acids rich diet (100% sunflower oil) or w-3 fatty acids fortified diet (12% fish oil plus 88% sunflower oil) during 28 days. Twelve hours prior to sacrifice, the mice were treated with 2,4-ninitro-1-fluorobezene on the left ear to induce the inflammatory reaction. Afterwards the mice were sacrificed and the different samples collected were analized. RESULTS: Ear inflammation of mice fed the w-3 diet was significantly lower. Leukocyte infiltration and oxidative stress were also lower in those mice. To explain these results, cytokine expression and plasma eicosanoid concentration were measured. An increase in IL-10 levels and a down regulation of Th1 and Th2 responses were observed in mice fed the w-3 diet. CONCLUSION: Not only n-3 fatty acids exerts an antiinflammatory and an antialergical role but also they enhance some of the organism defenses. Our data suggest that w-3 fatty acids downregulate the inflammatory response by enhancing IL10 expression.

Animals↗