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Biomedical subjects

N Martínez

Publications and source records attributed to N Martínez.

At least 19 recordsLinked to original sources
PubMed2006

PPARdelta and its activator PGI2 are reduced in diabetic embryopathy: involvement of PPARdelta activation in lipid metabolic and signalling pathways in rat embryo early organogenesis.

Maternal diabetes significantly increases the risk of congenital malformations, and the mechanisms involved are not yet clarified. This study was designed to address peroxisome proliferator-activated receptor delta (PPARdelta) involvement in diabetic embryopathy. We investigated the concentrations of PPARdelta and its endogenous agonist prostaglandin (PG)I(2), as well as the effect of PPARdelta activation on lipid metabolism and PGE(2) concentrations in embryos from control and streptozotocin-induced diabetic rats during early organogenesis. Embryos from diabetic rats showed decreased concentrations of PPARdelta and its endogenous agonist PGI(2) when compared with controls. In embryos from control rats, the addition of the PPARdelta activators (cPGI(2) and PGA(1)) increased embryonic phospholipid levels and de novo phospholipid synthesis studied using (14)C-acetate as a tracer. PGE(2) formed from arachidonate released from phospholipid stores was also up-regulated by PPARdelta activators. In embryos from diabetic rats, reduced phospholipid synthesis and PGE(2) content were observed, and clearly up-regulated by cPGI(2) additions to values similar to those found in control embryos. These data suggest that PPARdelta may play an important role in lipid metabolic and signalling pathways during embryo organogenesis, developmental pathways that are altered in embryos from diabetic rats, possibly as a result of a reduction in levels of PPARdelta and its endogenous activator PGI(2).

Animals↗
PubMed2005

Peroxynitrites and impaired modulation of nitric oxide concentrations in embryos from diabetic rats during early organogenesis.

Maternal diabetes significantly increases the risk of congenital malformation, a syndrome known as diabetic embryopathy. Nitric oxide (NO), implicated in embryogenesis, has been found elevated in embryos from diabetic rats during organogenesis. The developmental signaling molecules endothelin-1 (ET-1) and 15-deoxy delta(12,14)prostaglandin J2 (15dPGJ2) downregulate embryonic NO levels. In the presence of NO and superoxide, formation of the potent oxidant peroxynitrite may occur. Therefore, we investigated peroxynitrite-induced damage, ET-1 and 15dPGJ2 concentrations, and the capability of ET-1, 15dPGJ2 and prostaglandin E2 (PGE2) to regulate NO production in embryos from severely diabetic rats (streptozotocin-induced before pregnancy). We found intense nitrotyrosine immunostaining (an index of peroxynitrite-induced damage) in neural folds, neural tube and developing heart of embryos from diabetic rats (P < 0.001 vs controls). We also found reduced ET-1 (P < 0.001) and 15dPGJ2 (P < 0.001) concentrations in embryos from diabetic rats when compared with controls. In addition, the inhibitory effect of ET-1, 15dPGJ2 and PGE2 on NO production found in control embryos was not observed in embryos from severely diabetic rats. In conclusion, both the demonstrated peroxynitrite-induced damage and the altered levels and function of multiple signaling molecules involved in the regulation of NO production provide supportive evidence of nitrosative stress in diabetic embryopathy.

Animals↗
PubMed2004

[Evaluation of a pharmaceutical care program to improve adherence to antiretroviral therapy].

OBJECTIVE: To establish the impact of a pharmaceutical care program on the improvement of adherence to antiretroviral therapy, and on patient immunologic and virologic outcome. MATERIALS AND METHODS: A multicenter, observational, prospective study in a HIV-infected patient cohort under treatment with antiretrovirals selected by random sampling in 19 Spanish hospitals. The study lasted 12 months, in which the program was applied through a baseline preprocedural visit and 4 quarterly visits. Adherence estimation was based on pill counting. An adherence > or = 90, or > or = 95% was considered adequate (in two time points). RESULTS: 541 patients were included, most of them were males (68.8%) between 20 and 78 years of age. Major risk groups included injecting drug users (43.4%) and heterosexuals (29.4%). Sixty percent had already received treatment for more than 3 years. Mean baseline viral load and CD4 count values were 32,866 copies/ml and 485 cells/mm3, respectively. Throughout the study a slight increase in the percentage of adherent patients was seen; however, statistical significance was not reached (64.3 and 79.2% of patients showed an adherence > 95 and > 90%, respectively, during the fourth quarter, versus 59.8 and 75.5% at baseline). A statistically significant decrease in viral load and increase in CD4 cells was seen following program application. The percentage of patients with a viral load < 200 copies/ml was 72.2, 76.7, and 75.0% at the 2nd, 3rd, and 4th quarters, respectively, versus 64.2% at baseline. CD4 cell counts increased by 50 cells/mm3 on average from the start to the end of follow-up. CONCLUSIONS: Patients included in the program had a good immunologic and virologic outcome, and a trend towards an increased percentage of patients with good adherence was also seen. These results confirm the need to implement follow-up programs for patients receiving antiretrovirals in order to ensure maximum therapeutic benefits.

Adult↗
PubMed2000

N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria.

Mitochondrial oxidative damage is implicated in brain aging and in age-related neurodegenerative diseases. Since N-acetylcysteine (NAC) has recently been shown to prevent apoptotic death in neuronal cells and protect synaptic mitochondria proteins from oxidative damage in aged mice, we have investigated whether dietary administration of this thiolic antioxidant retards age-related memory loss. At 48 weeks of age, a control female OF-1 mice group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of NAC. After 23 weeks of this diet, the NAC had partially restored the memory deficit associated with aging in mice. Moreover, the lipid peroxide and protein carbonyl contents of the synaptic mitochondria were significantly decreased in the NAC-supplemented animals in comparison with their age-matched controls. The antioxidant properties and probable action on mitochondrial bioenergetic ability in the synaptic terminals may explain, at least partially, the beneficial action of NAC administration.

Acetylcysteine↗
PubMed2000

Usefulness of genetic typing methods to trace epidemiologically Salmonella serotype Ohio.

Different genetic typing procedures were applied in an epidemiological study of Salmonella serotype Ohio. Isolates that generated identical DNA fingerprints (HinclI ribotypes, ERIC and RAPD profiles) were clustered into the same lineage, and the addition of data from plasmid, integron and resistance profiles was used to differentiate types. Results led to the determination of the endemic and the emergent epidemic types at specific times, and to ascertain the clinical and epidemiological impact of each type. In the series analysed (47 clinical isolates and 3 non-clinical isolates) 11 lineages and 32 types were found. Two lineages were considered prevalent and endemic, and during an epidemiological alert (Spain, 1998) a re-emergence and spread of organisms mainly from the most frequent lineage had occurred. The combination of H-ribotype with ERIC profile, as primary markers, and resistance profile with plasmid profile, as secondary markers, was shown to be the most useful tool to trace epidemiologically Ohio.

Adolescent↗
PubMed2000

In vivo effects of CGP-12177 on the expression of leptin and uncoupling protein genes in mouse brown and white adipose tissues.

OBJECTIVE: To assess the effect of chronic treatment with CGP-12177 a beta3-adrenergic receptor (AR) agonist with beta2/beta1-AR antagonist action, on the expression of the leptin gene and of genes coding for uncoupling proteins (ucp1, ucp2 and ucp3) in brown and white adipose tissues. DESIGN: NMRI mice received a daily subcutaneous injection of CGP-12177 at a dose of 0.05, 0.2, 0.5 or 1 mg/kg for 15 days. The specific levels of the mRNAs of interest were analysed in interscapular brown adipose tissue (BAT) and in two white adipose tissue (WAT) depots, inguinal (IWAT) and epididymal (EWAT). RESULTS: No changes in food intake or body weight were detected at any dose of CGP-12177. In the two WAT depots, the treatment led to enhanced expression of ucp1 and ucp3, but not of ucp2. In BAT, low doses (0.05 and 0.2 mg/kg) led to a decreased expression of the three ucp genes, whereas a slight stimulatory effect on the three ucp genes was elicited with a high dose (1 mg/kg). Treated animals displayed increased expression of leptin in BAT and, to a lesser extent, in IWAT, but not in EWAT. CONCLUSION: The results reveal that simultaneous stimulation of the expression of certain ucp genes and the leptin gene can be achieved, and suggest that adrenergic regulation of the leptin gene and of genes of the ucp family in adipose tissues is the result of complex interactions between the different beta-AR pathways.

Adipose Tissue↗
PubMed2000

nm23-H1 expression defines a high-risk subpopulation of patients with early-stage epithelial ovarian carcinoma.

The role of the nm23 gene in human ovarian cancer is still controversial. We studied the expression of the nm23-H1 gene in 247 human epithelial ovarian carcinomas. The patients were followed-up until their death, or for a minimum of 5 years if they survived. The expression of the gene was studied by means of immunohistochemistry and a semiquantitative scoring system considering the staining intensity and the number of reactive tumour cells. Patients carrying tumours with higher expression scores (4-6 on a scale from 0 to 6) had a significantly lower survival (P = 0.01) than the rest. Further stratified statistical analysis revealed that this effect was mainly attributable to the subgroup of patients with early-stage (I and II), well- and moderately differentiated tumours. In fact, a multivariate analysis carried out for this subset of patients showed nm23-overexpression to be the only significant independent predictor of an ominous prognosis. The association of nm23-overexpression with a worse prognosis was most probably not due to mutation of the nm23 gene, since mutational analysis in 60 tumours by means of single-strand conformational polymorphism and direct sequencing disclosed only one mutation, which was located outside the open reading frame. Our results seem to indicate that nm23 expression is associated with a significantly worse prognosis in early-stage, well-differentiated epithelial ovarian carcinoma, a finding with important clinical implications, considering that many patients with ovarian cancers showing these features do not undergo any further treatment beyond surgical staging. If confirmed, they could help in tailoring the treatment of these patients in the future.

Aged↗
PubMed1999

EGFR family-mediated signal transduction in the human keratinocyte cell line HaCaT.

We analyzed the formation of homo- and heterodimers between EGFR, ErbB2, and ErbB3 (members of the EGF receptor family) in the human skin keratinocyte cell line HaCaT, in dependence of the added ligand. ErbB4 was not unambiguously identified. By immunoprecipitation and Western blots, we showed the formation of heterodimers between all members of the family. Whereas EGF and TGF-alpha strongly induced heterodimerization, no effect was observed with heregulin. At the concentrations used all ligands elicited a similar, differentiation-independent activation of erk1/2 MAP kinase, with the exception of heregulin which activated p42/44 only marginally. We also found that different ligands triggered different transcription patterns of "early genes," with the exception of heregulin which did not modulate transcription. TGF-alpha was the most efficient ligand in promoting incorporation of tritiated thymidine into the DNA.

Cell Line↗
PubMed1999

The nuclear pore complex protein Nup88 is overexpressed in tumor cells.

It has been previously shown (J. Schneider et al., Br. J. Cancer, 77: 1015-1020, 1998) that an antibody directed against Candida albicans proteins (C6) recognizes specifically a protein in human ovarian tumors. We have now performed an immunoscreening of a human cDNA library using this antibody and identified the antigen as Nup88, a protein localized preferentially at the nuclear membrane and probably implicated in nucleocytoplasmic transport. Our results show that Nup88 is strongly expressed in a series of human tumor cell lines compared with nontransformed cell lines at the RNA and the protein levels. Furthermore, we observed that in 76% of 21 ovarian tumors analyzed, the protein is also overexpressed in malignant tissue when compared with healthy adjacent tissue. Nup88 may, therefore, be considered as a putative marker for tumor growth and is probably related to increased cell cycling.

Antibodies, Monoclonal↗
PubMed1999

N-acetylcysteine elicited increase in cytochrome c oxidase activity in mice synaptic mitochondria.

It has been suggested that thiolic groups are essential for cytochrome c oxidase (COX) activity and other respiratory mitochondrial enzymes. Recent experiments showed that the thiolic antioxidant N-acetylcysteine (NAC) can protect against age-related impairment in COX activity in mice hepatic mitochondria. The present paper shows that NAC enhances COX activity in vitro in synaptic mitochondria isolated from young and old mice. The optimum NAC concentration for maximum COX activity was 5 mM in young and 10 mM in old synaptic preparations. Our data suggest that mitochondrial thiolic groups, which are essentials to oxidative phosphorylation, are impaired by aging.

Acetylcysteine↗
PubMed1999

Hypothesis: can N-acetylcysteine be beneficial in Parkinson's disease?

Based on the finding of decreased mitochondrial complex I activity in the substantia nigra of patients with Parkinson's disease, we propose that the consequent reduction of ATP synthesis and increased generation of reactive oxygen species may be a possible cause of nigrostriatal cell death. Since sulfhydryl groups are essential in oxidative phosphorylation, thiolic antioxidants may contribute to the preservation of these proteins against oxidative damage. In the present paper, we hypothesize that treatment with a sulfur-containing antioxidant such as N-acetylcysteine may provide a new neuroprotective therapeutic strategy for Parkinson's disease.

Acetylcysteine↗
PubMed1999

Pyodermatitis-pyostomatitis vegetans: report of a case and review of the literature.

Pyodermatitis-pyostomatitis vegetans is a benign, rare disorder characterized by a pustular eruption in the oral mucosa and vegetating plaques involving the groin and axillary folds. Its association with inflammatory bowel disease is well established. We report the case of a 49-year-old-white man with ulcerative colitis who manifested a vegetating, annular plaque in the left inguinal region of 2 months' duration. Oral examination disclosed an erythematous mucosa with multiple painful pustules involving the labial and gingival mucosa. Histopathologic study demonstrated epidermal hyperplasia and an inflammatory infiltrate composed mostly of neutrophils and eosinophils, grouped into microabscesses within the epidermis and with a bandlike configuration in the upper dermis. Results of direct and indirect immunofluorescence studies were negative. We discuss the differential diagnosis between pyodermatitis-pyostomatitis vegetans and pemphigus vegetans.

Anti-Inflammatory Agents↗
PubMed1998

Cross-reactivity between Candida albicans and human ovarian carcinoma as revealed by monoclonal antibodies PA10F and C6.

Summary Antibodies against Candida albicans antigenic determinants have been reported to cross-react with human tumour cells. We have found that two monoclonal antibodies, C6 and PA1OF, developed at our laboratory against C. albicans antigenic determinants, cross-react with human ovarian cancer on Western blots and immunohistochemistry. We have subsequently used one of them, PA10OF, to test by means of immunohistochemistry a series of 37 human ovarian carcinomas. Out of 37 tumours, 25 (67.6%) expressed the antigen recognized by PA1OF. The reactivity, however, was concentrated on the subgroup of particularly aggressive, invasive carcinomas in advanced stages of the disease (19 out of 24 positive), whereas the antigen was expressed significantly less (P=0.0007) in the subgroup of much less aggressive stage I tumours of low malignant potential, also called borderline carcinomas (2 out of 13 positive). This cross-reactivity between C. albicans and ovarian carcinoma seems to be attributable to a common antigenic determinant related to tumour aggressiveness.

Animals↗
PubMed1997

N-acetylcysteine protects against age-related increase in oxidized proteins in mouse synaptic mitochondria.

Since it has been proposed that oxidized protein accumulation plays a critical role in brain aging, we have investigated the effect of a thiolic antioxidant on protein carbonyl content in synaptic mitochondria from female OF-1 mice. At 48 weeks of age, a control group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of N-acetylcysteine. A 24-week treatment resulted in a significant decrease in protein carbonyl content in synaptic mitochondria of the N-acetylcysteine-treated animals as compared to age-matched controls.

Acetylcysteine↗
PubMed1996

Age-related increase in oxidized proteins in mouse synaptic mitochondria.

Since it has been proposed that oxidized protein accumulation plays a critical role in brain aging, we have investigated their contents in synaptic mitochondria from five age groups of mice. Protein carbonyl content in synaptic mitochondria showed a significant positive correlation with age (r = 0.95, P = 0.01). A linear inverse relationship was observed between protein carbonyl content and complex IV/complex I ratio (which was used as an index of imbalance between mitochondrial respiratory complexes) in synaptic mitochondria in the five age groups (r = -0.99, P < 0.001). We suggest that age-related accumulation of oxidized proteins in synaptic mitochondria may be the result of an age-dependent increase in reactive oxygen species generation because of a disarrangement of mitochondrial oxidative phosphorylation.

Aging↗
PubMed1996

Immunocharacterization of Taenia solium oncosphere and metacestode antigens.

A partial immunocharacterization of oncosphere and metacestode antigens of Taenia solium was carried out and compared to antigens from other taeniid species. The results indicated that T. solium metacestode antigen contained epitopes cross reactive with rabbit anti-sera to adult and oncospheral stages of the parasite. Oncospheres, however, consisted largely of stage specific antigens. Western blot analysis indicated that T. solium and T. pisiformis shared several oncospheral antigens; however, this was not the case with T. solium and T. hydatigena. Western blot analysis showed a time-related increase in the number of molecules recognized by antibodies to T. solium oncosphere and metacestode antigens in pigs experimentally infected with T. solium eggs. Oncosphere specific antibodies were detected in pig sera one month after experimental infection whereas antibodies to cystic stage antigens were not present until the 3rd to 5th month post infection. Sera from neurocysticercotic patients as well as naturally infected cysticercotic pigs recognized high molecular weight antigens in the oncospheres.

Animals↗