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Biomedical subjects

E Navarro

Publications and source records attributed to E Navarro.

At least 19 recordsLinked to original sources
PubMed2000

Overexpression of the crgA gene abolishes light requirement for carotenoid biosynthesis in Mucor circinelloides.

This work describes the isolation and characterization of crgA, a Mucor circinelloides gene, which has a dominant-positive effect on light-regulated carotenogenesis. The crgA gene was originally identified in a transformation experiment as a 3'-truncated open reading frame which caused carotenoid overaccumulation in the dark. The complete cloning and sequencing of crgA revealed that its putative product presented several recognizable structural domains: a RING-finger zinc binding domain near the N-terminus, a putative nuclear localization signal, two stretches of acidic amino acids, glutamine-rich regions and a putative isoprenylation motif. The expression of exogenous copies of the complete crgA gene or two different 3'-truncated versions, produced a similar dominant-positive effect on the light-inducible carotenogenesis of M. circinelloides. The presence of these exogenous sequences also caused a missregulation of the endogenous crgA gene, resulting in its overexpression. Collectively, these observations suggest that crgA is involved in the regulation of carotenoid biosynthesis by light.

Amino Acid Sequence↗
PubMed2000

Randomized comparative trial of triflusal and aspirin following acute myocardial infarction.

AIMS: To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction. METHODS AND RESULTS: In this double-blind, multicentre, sequential design study, patients were randomized within 24 h of acute myocardial infarction symptom onset to receive triflusal 600 mg or aspirin 300 mg once daily for 35 days. The primary end-point was death, non-fatal myocardial reinfarction or a non-fatal cerebrovascular event. The incidences of these individual outcomes and urgent revascularization were secondary end-points. The null hypothesis of no difference between treatments in the primary combined end-point was accepted with 80% power after recruiting 2124 validated patients (odds ratio (OR) for failure [95% confidence interval (CI)]: 0.882 [0.634-1.227]). Non-fatal cerebrovascular events were significantly less frequent with triflusal (OR [95% CI]: 0.364 [0.146-0.908]; P = 0.030). There was no significant difference between treatments for death (OR [95% CI]: 0.816 [0.564-1.179]; P = 0.278), non-fatal reinfarction (OR [95% CI]: 1.577 [0.873-2.848]; P = 0.131) or revascularization (OR [95% CI]: 0.864 [0.644-1.161]; P = 0.334). Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0.27% vs. 0.97%; P = 0.033). CONCLUSION: Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile. Triflusal significantly reduced the incidence of non-fatal cerebrovascular events compared with aspirin.

Aged↗
PubMed2000

Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis.

BACKGROUND: Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated. AIMS: To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E(2) formation in male Sprague-Dawley rats with azoxymethane induced colon cancer. METHODS: Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE(2) were assessed at week 12, and tumour formation at week 19. RESULTS: Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE(2) formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets. CONCLUSIONS: Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE(2) synthesis.

Adenocarcinoma↗
PubMed2000

Abnormal fatty acid pattern in rheumatoid arthritis. A rationale for treatment with marine and botanical lipids.

OBJECTIVE: To assess the fatty acid pattern in plasma and synovial fluid (SF) in rheumatoid arthritis (RA) and to determine clinical factors related to possible abnormalities. METHODS: Thirty-nine patients with RA were included. SF samples were obtained from 9 patients. Disease activity was assessed using the Ritchie Articular Index and erythrocyte sedimentation rate. Fatty acids were assayed with gas liquid chromatography. RESULT: Decreased levels of eicosapentaenoic acid (p < 0.0001) and total n3 polyunsaturated fatty acids (p < 0.05) were observed in plasma and in joint fluid, respectively. An increase of the substrates of delta-5-desaturase (C20:3n6 and C20:2n6) and decrease of their products (C20:4n6 and C22:4n6) was observed in plasma total lipids and phospholipids. The long chain mono-unsaturated fatty acids (C20: 1n9, C22: 1n9, C24: ln9) were increased in the joint fluid and in plasma phospholipids. Patients with active disease showed a mild decrease of several saturated fatty acids, n3, and n6 polyunsaturated fatty acids. Minor abnormalities or no changes in fatty acid profile were found related to use of steroids, nonsteroidal antiinflammatory drugs, and gold salts, or malnutrition. CONCLUSION: The fatty acid pattern found in RA (decreased levels of n3 polyunsaturated fatty acids) may explain the beneficial effect of fish oil. Changes in n6 polyunsaturated fatty acids suggest that delta-5 desaturation is decreased and this might facilitate the antiinflammatory effect of botanical lipids in RA.

Aged↗
PubMed1999

Expressed sequence tag (EST) phenotyping of HT-29 cells: cloning of ser/thr protein kinase EMK1, kinesin KIF3B, and of transcripts that include Alu repeated elements.

To study the mechanisms that control epithelial commitment and differentiation we have used undifferentiated HT-29 colon cancer cells and a subpopulation of mucus secreting cells obtained by selection of HT-29 cells in 10-6 M methotrexate (M6 cells) as experimental models. We isolated cDNAs encoding transcripts overexpressed in early confluent M6 cells regarding steady-state levels in HT-29 cells by subtractive hybridisation. Fifty-one cDNA clones, corresponding to 34 independent transcripts, were isolated, partially sequenced by their 5' end, and classified into four groups according to their identity: transcripts that included a repeated sequence of the Alu family (10 clones, among them those encoding ribonucleoprotein RNP-L and E-cadherin), transcripts encoded by the mitochondrial genome (nine clones), transcripts encoding components of the protein synthesis machinery (23 clones, including the human ribosomal protein L38 not previously cloned in humans) and nine additional cDNAs that could not be classified in the previous groups. These last included ferritin, cytokeratin 18, translationally controlled human tumour protein (TCHTP), mt-aldehyde dehydrogenase, as well as unknown transcripts (three clones), and the human homologues of the molecular motor kinesin KIF3B and of the ser/thr protein kinase EMK1. Spot dot and Northern blot analyses showed that ser/thr protein kinase EMK1 was differentially expressed in M6 cells when compared with parental HT-29 cells. Steady-state levels of EMK1 were higher in proliferating, preconfluent, M6 and HT-29 cells than in 2 days post confluence (dpc) and 8dpc M6 and HT-29 cells. Transcripts that included an Alu repeat were also shown to be differentially expressed and accumulated in differentiating M6 cells when analysed by Northern blot. The significance of the transcripts cloned is discussed in the context of the commitment and differentiation of the M6 cells to the mucus secreting lineage of epithelial cells.

Alu Elements↗
PubMed1999

Distribution of gymnostoma spp. microsymbiotic frankia strains in new caledonia is related to soil type and to host-plant species

The diversity of the Frankia strains that are naturally in symbiosis with plants belonging to the Gymnostoma genus in New Caledonia was investigated. A direct molecular characterization of DNA extracted from nodules was performed, followed by characterization by restriction fragment length polymorphism (RFLP) of the ribosomal rrs-rrl (16S-23S) intergenic spacer (IGS) polymerase chain reaction (PCR)-amplified region. Seventeen different patterns were identified among the 358 microsymbiotic strains studied in the eight species of host plant present in New Caledonia. This genotypical approach permitted us to show that a large diversity existed among the patterns and that these did not exhibit a strict specificity to any host-plant species comparable with that previously found in the Casuarina and Allocasuarina symbioses in Australia. Despite this lack of specificity, a correspondence analysis nevertheless showed that the distribution of these patterns was related to soil type and to host-plant species. Furthermore, several Frankia strains were exclusively associated with the ultramafic soils.

Journal Article↗
PubMed1999

Adherence of Candida albicans to bladder mucosa: development and application of a tissue explant assay.

In order to study the interactions between Candida species and uroepithelial tissue, a tissue explant assay was developed using bladder mucosa harvested from New Zealand white rabbits. Blastoconidia of Candida albicans, Candida tropicalis and Candida glabrata attached to the uroepithelial tissue in similar quantities. However, there was significantly more adherence to the uroepithelium by pre-germinated C. albicans compared with C. albicans blastoconidia. Furthermore, the amount of uroepithelial tissue injury was directly related to the length of exposure of the tissue to Candida. Thus, this tissue explant assay may provide a useful method for investigating properties related to fungal adherence to transitional uroepithelium and organism-mediated tissue injury.

Animals↗
PubMed1999

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU).

OBJECTIVE: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate, the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. METHODS: An open label, parallel-group, multicenter, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 mg t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. RESULTS: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. CONCLUSIONS: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis.

Adult↗
PubMed1999

Fungal lethality, binding, and cytotoxicity of syringomycin-E.

Syringomycin-E (SE) was significantly lethal to Aspergillus and Fusarium species at between 1.9 and 7.8 micrograms/ml. SE complexed with the following fungal wall constituents (in order of binding): beta-1,3-glucan > chitin > mannan > ergosterol = cholesterol. Cytotoxicity in HeLa cells was proportional to the SE concentration, while the amount required for cytotoxicity was 3 to 20 times that needed to kill 95% of the fungi tested.

Antifungal Agents↗
PubMed1999

Action of antidepressant drugs on maternal stress-induced hypoactivity in female rats.

It has been reported that rats forced to swim in a restricted space assume, after initial frenzied attempts to escape, an immobile posture. Porsolt et al. referred to this phenomenon as "behavioral despair", an animal model of depression. Prenatal stress induces an increase of behavioral depression in adult female offspring. This study presents new evidence supporting the hypothesis that maternal stress during gestation increases the risk of depression in the offspring since immobility time was modified by antidepressant drugs (tricyclics and an atypical antidepressant). In rats, amitriptyline (5 mg/kg), imipramine (5 mg/kg) and nomifensine (1 mg/kg) decreased the immobility time in Porsolt test in offspring of mothers stressed during gestation. Moreover, increasing doses of amitriptyline (1, 5, 25 and 40 mg/kg) reduced depression in the forced swimming test in dose-dependent manner.

Amitriptyline↗
PubMed1999

High prevalence of the C634Y mutation in the RET proto-oncogene in MEN 2A families in Spain.

The RET proto-oncogene encodes a receptor tyrosine kinase expressed in neural crest derived tissues. Germline mutations in the RET proto-oncogene are responsible for three different dominantly inherited cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). MTC can also occur sporadically. Molecular characterisation of the RET proto-oncogene has been performed by PCR-SSCP analysis, direct DNA sequencing, and restriction enzyme analysis in 49 unrelated, Spanish, MEN 2 families: 30 MEN 2A families, six FMTC families, and 13 families classified as "other". Germline missense mutations in one of six cysteine codons (609, 611, 618, and 620 in exon 10, and codons 630 and 634 in exon 11), which encode part of the extracellular cysteine rich domain of RET, have been detected in the majority of these families: 100% of MEN 2A families, 67% of FMTC families, and 54% of families classified as "other". No RET mutations in exons 10, 11, 13, 14, 15, or 16 were detected in the remaining families. The most frequent RET mutation in MEN 2A Spanish families is C634Y, occurring in 73% of cases. Haplotype analysis does not exclude the possibility of founder effects in Spanish MEN 2A families with the C634Y mutation.

Chromosomes, Human, Pair 1↗
PubMed1998

Radioactivity measurements on migrating birds (Turdus philomelos) captured in the Comunidad Valenciana (Spain).

The radionuclides 137Cs, 134Cs and 90Sr have been measured in edible tissues and bones of migratory birds (song-thrushes, Turdus philomelos) from central and northern Europe and captured in the Comunidad Valenciana, Spain in the 1994 autumn-winter season. Eight years after the Chernobyl accident, extensive agricultural lands in Europe are still contaminated and this study shows that there was a transfer of radioactive isotopes to the captured migratory song-thrushes. The whole-body dose commitment to humans consuming these birds is estimated.

Agriculture↗
PubMed1998

Plasma and mucosal fatty acid pattern in colectomized ulcerative colitis patients.

Patients with inflammatory bowel disease (IBD) have increased plasma n3 polyunsaturated fatty acids (PUFAs), which in ulcerative colitis (UC) patients persists six months after colectomy, suggesting a primary abnormality in fatty acid (FA) metabolism in IBD. This finding needed to be confirmed in a larger series of UC long-term colectomized patients. We aimed to assess the plasma FA pattern in UC colectomized patients with either Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA) and the mucosal FA pattern in the ileal reservoir of the UC-IPAA patients. Plasma FAs were assessed in 63 UC colectomized patients (31 with BI and 32 with IPAA) and 30 controls. In 26 UC-IPAA (8 with pouchitis and 18 without pouchitis) and in 13 healthy controls gut mucosal FAs were also investigated. FAs were detected by capillary column gas-liquid chromatography. Increased levels of saturated fatty acids (SFAs) and decreased percentages of monounsaturated fatty acids (MUFAs) were observed in both groups of patients. There were no changes in plasma n3 and n6 PUFAs. The mucosal FA pattern of the ileal reservoir consisted of increased long-chain PUFAs, specially n6 PUFA, and a decrease of their essential precursors. High percentages of SFAs and low percentages of MUFAs were also seen. The plasma FA profile previously described in IBD is not observed long-term after colectomy in UC, suggesting that it is related with the presence of inflamed intestine. High concentrations of SFAs and decreased percentages of MUFAs might represent early events in disturbed FA metabolism in IBD. The changes in FAs of the ileal reservoir, which closely resemble those found in human and experimental IBD, probably represent a common pattern of intestinal inflammation.

Adult↗
PubMed1998

Conception after iodine-131 therapy for differentiated thyroid cancer.

We reviewed the medical history of 26 women with differentiated thyroid cancer who became pregnant after receiving therapeutic doses of radioactive iodine (131I) in order to document the possibility of a greater risk for disorders in these pregnancies. There were a total of 39 pregnancies, 6 of which occurred during the first year after therapy. In 3 cases the following anomalies were encountered: a male suffering Trisomy 18 (Edward's syndrome), a female with constitutional aplastic anemia, and a male with a congenital hip dysplasia. Of the 33 pregnancies that occurred after the first year post-therapy, there were 2 spontaneous abortions and a male effected by ureteral stenosis. Based on these data, although it cannot be confirmed that these congenital disorders are due to the 131I therapy, we recommend that pregnancy be avoided for the first year after therapy.

Abortion, Spontaneous↗