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Biomedical subjects

E Espinosa

Publications and source records attributed to E Espinosa.

At least 37 records · Page 2Linked to original sources

Introduction of heteroatom-based substituents into 1,4-dihydropyridines by means of a halogen-mediated, oxidative protocol: diamination, sulfonylation, sulfinylation, bis-sulfanylation, and halo-phosphonylation processes

The natural tendency of 1,4-dihydropyridines to undergo "biomimetic" oxidation to afford pyridinium salts can be switched off and, through the use of reagents that interact electrophilically with the enamine moiety present in the heterocyclic system, it is possible to promote alternative oxidations. In this way, efficient regio- and stereocontrolled synthetic methods have been developed that lead to diversely substituted di- and tetrahydropyridines. These include iodoazidation, diamination, bis-sulfonamidation, sulfonylation, sulfinylation, thiocyanation, sulfanylation, bis-sulfanylation, and halo-phosphonylation processes.

Journal Article↗

Failure of goserelin ovarian ablation in premenopausal women with breast cancer: two case reports.

OBJECTIVE: We hereby report on two patients receiving goserelin due to breast cancer in whom a failure in ovarian ablation was detected. A review of the hormonal effects of LHRH analogues is performed. CASE REPORTS: CASE 1: A 36-year-old female was diagnosed with breast carcinoma and treated with surgery, chemotherapy, radiotherapy, and goserelin. A 16-week gestation was detected after 17 months of uninterrumpted hormonal therapy at ablative doses. CASE 2: A 41-year-old female was diagnosed with breast carcinoma and treated with surgery, chemotherapy, radiotherapy, and tamoxifen. Goserelin was substituted for tamoxifen due to bone metastases and, 2 years later, a failure in ovarian ablation was confirmed after the reappearance of the patient's menses. CONCLUSIONS: Goserelin-induced ovarian ablation may fail after the use of appropriate doses of this drug. We suggest a possible mechanism of hormone resistance induced by the long-term administration of LHRH analogues. No fetal damage was detected after goserelin exposure in the first 4 months of gestation.

Adult↗

Pregnancy in a breast cancer patient treated with a LHRH analogue at ablative doses.

A 36-year-old female diagnosed of breast cancer was treated with surgery, chemotherapy, radiotherapy and goserelin. After 17 months of uninterrupted therapy with this LHRH analogue at hormone suppressive doses, a 16-week gestation foetus was detected and the treatment was withdrawn. Although the drug was administered throughout the first 4 months of pregnancy it resulted in the term delivery of a healthy infant, and no foetal adverse effects were detected. A review of the influence of hormonal treatment for breast cancer on fertility and birth defects has been performed.

Journal Article↗

3-Formyl-1-butyl pyrophosphate A novel mycobacterial metabolite-activating human gammadelta T cells.

Most human blood gammadelta T cells react without major histocompatibility complex restriction to small phosphorylated nonpeptide antigens (phosphoantigens) that are abundantly produced by mycobacteria and several other microbial pathogens. Although isopentenyl pyrophosphate has been identified as a mycobacterial antigen for gammadelta T cells, the structure of several other stimulating compounds with bioactivities around 1000-fold higher than isopentenyl pyrophosphate remains to be elucidated. This paper describes the structural identification of 3-formyl-1-butyl-pyrophosphate as the core of several non-prenyl mycobacterial phosphoantigens bioactive at the nM range. Recognition of this molecule by gammadelta T cells is very selective and relies on its aldehyde and pyrophosphate groups. This novel pyrophosphorylated aldehyde most probably corresponds to a metabolic intermediate of the non-mevalonate pathway of prenyl phosphate biosynthesis in eubacteria and algae. The reactivity to 3-formyl-1-butyl-pyrophosphate supports the view that human gammadelta T cells are physiologically devoted to antimicrobial surveillance.

Antigens, Bacterial↗

Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group.

BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.

Age Factors↗

Topological analysis of the electron density in hydrogen bonds.

Topological analysis of the experimental electron density rho(r) in hydrogen-bonding regions has been carried out for a large number of organic compounds using different multipole models and techniques. Relevant systematic relationships between topological properties at the critical points and the usual geometric parameters are pointed out. Results involving X-ray data only and joint X-ray and neutron data, as well as special hydrogen bonding cases (symmetric, bifurcated, peptide bonds, etc.) are included and analysed in the same framework. A new classification of hydrogen bonds using the positive curvature of the electron density at the critical point [lambda(3)(r(CP))] is proposed.

Journal Article↗

Low calorie diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives.

The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P<0.01), which was accompanied by increase of cGMP excretion (from 146.0+/-10.1 to 154.5+/-9.5 nmol/24 h; P<0.05) together with a reduction of BP (P<0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, -6.4+/-0.7 versus -4. 0+/-0.6 mm Hg; P<0.05) as well as that of aldosterone (P<0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction.

Aldosterone↗

[Antineutrophil cytoplasmic antibodies in patients with sickle cell anemia].

PURPOSE: To determine whether anti neutrophil cytoplasmic antibodies (ANCA): anti myeloperoxidase (anti MPO) and anti proteinase 3 (anti PR3), are present in patients with sickle cell anaemia (SCA) during painful crisis. PATIENTS AND METHODS: 55 patients with SCA were included in this study, 35 of them had painful crisis and the rest were in steady state. We determined levels of anti MPO and anti PR3 by two enzyme immunoassays commercially available (Progen Biotechnik GMBH). RESULTS: A significant increase of anti MPO in the group of patients with painful crisis was found in comparison with steady state patients and controls. CONCLUSIONS: Our results suggest the possibility that anti MPO interacting with MPO on primed neutrophils lead to neutrophil activation, enhanced neutrophil adhesion and amplification of endothelial cell damage.

Adolescent↗

Effect of mare's age and recovery methods on the recovery rate of equine follicular oocytes for IVM procedures.

Mares (n = 39) were classified according to age as young (less than 1.5 yr, n = 17) or old (more than 1.5 yr, n = 22) and sacrificed. Ovaries were measured and weighed, and the number of follicles and CL were counted. Follicle size and distribution were recorded (external: > 20 mm, < 20 mm; internal: > 5 mm, < 5 mm). External follicles were aspirated while internal follicles were sliced. The number and Type of oocytes recovered using each method were recorded. Oocyte recovery rates (oocytes/ovary) resulted in a mean of 0.92 oocytes by aspiration and 1.36 oocytes by additional slicing. The mean numbers of available follicles (8.11 and 5.02) oocytes recovered (4.94 and 3.02) and oocytes selected per ovary (3.29 and 2.32) were not significantly different in the young or old mares, respectively.

Animals↗

Mapping diplosporous apomixis in tetraploid Tripsacum: one gene or several genes?

Polyploids in Tripsacum, a wild relative of maize, reproduce through the diplosporous type of apomixis, an asexual mode of reproduction through seeds. Diplosporous apomixis involves both the failure of meiosis and the parthenogenetic development of the unreduced gametes, resulting in progenies that are exact genetic copies of the mother plant. Apomixis is believed to be controlled by one single dominant allele, responsible for the whole developmental process. Construction of a linkage map for the chromosome controlling diplosporous apomixis in Tripsacum was carried out in both tetraploid-apomictic and diploid-sexual Tripsacum species using maize restriction fragment length polymorphism (RFLP) probes. A high level of collinearity was observed between the Tripsacum chromosome carrying the control of apomixis and a duplicated segment in the maize genome. In the apomictic tetraploid, there was a strong restriction to recombination, as compared to the corresponding genomic segment in sexual plants and maize. This suggests that apomixis, although inherited as a single Mendelian allele, might really be controlled by a cluster of linked loci. The analysis also revealed the tetrasomic nature of the inheritance of the chromosomal segment controlling apomixis, which contradicts the usually accepted hypothesis of an allopolyploid origin of apomictic species. The implications of these data for the transfer of apomixis into cultivated crops are discussed, and a new approach to studying the genetics of apomixis, based on comparative mapping, is proposed.

Chromosome Mapping↗

Non-Mendelian transmission of apomixis in maize-Tripsacum hybrids caused by a transmission ratio distortion.

Apomixis is a mode of asexual reproduction through seeds. The apomictic process bypasses both meiosis and egg cell fertilization, producing offspring that are exact genetic replicas of the mother plant. In the Tripsacum agamic complex, all polyploids reproduce through the diplosporous type of apomixis, and diploids are sexual. In this paper, molecular markers linked with diplospory were used to analyse various generations of maize-Tripsacum hybrids and backcross derivatives and to derive a model for the inheritance of diplosporous reproduction. The results suggest that the gene or genes controlling apomixis in Tripsacum are linked with a segregation distorter-type system promoting the elimination of the apomixis alleles when transmitted through haploid gametes. Hence, this model offers an explanation of the relationship between apomixis and polyploidy. The evolutionary importance of this mechanism, which protects the diploid level from being invaded by apomixis, is discussed.

Chimera↗