Biomedical subjects

S Aznar

Publications and source records attributed to S Aznar.

13 recordsLinked to original sources

PubMed2006

Exacerbated loss of cell survival, neuropeptide Y-immunoreactive (IR) cells, and serotonin-IR fiber lengths in the dorsal hippocampus of the aged flinders sensitive line "depressed" rat: Implications for the pathophysiology of depression?

Impairment of hippocampal neurogenesis has been proposed to provide a cellular basis for the development of major depression. Studies have shown that serotonin (5-HT) and neuropeptide Y (NPY) may be involved in stimulating cell proliferation in the dentate gyrus. The Flinders-sensitive line (FSL) rat represents a genetic model of depression with characterized 5-HT and NPY abnormalities in the hippocampus. Consequently, it could be hypothesized that hippocampal neurogenesis in the FSL rat would be impaired. The present study examined the relationship among 1) number of BrdU-immunoreactive (IR) cells, 2) NPY-IR cells in the dentate gyrus, and 3) length of 5-HT-IR fibers in the dorsal hippocampus, as well as volume and number of 5-HT-IR cells in the dorsal raphé nucleus, in adult and aged FSL rats and control Flinders-resistant line (FRL) rats. Surprisingly, adult FSL rats had significantly more BrdU-IR and NPY-IR cells compared with adult FRL rats. However, aging caused an exacerbated loss of these cell types in the FSL strain compared with FRL. The aged FSL rats also had shortened 5-HT-IR fibers in the dorsal hippocampus, indicative of an impaired 5-HT innervation of this area, compared with FRL. These results suggest that, for "depressed" FSL rats, compared with FRL rats, aging is associated with an excacerbated loss of newly formed cells in addition to NPY-IR cells and 5-HT-IR dendrites in the hippocampus. These observations may be of relevance to the depression-like behavior of the FSL rat and, by inference, to the pathophysiology of depression.

Aging↗

PubMed2004

Non-serotonergic dorsal and median raphe projection onto parvalbumin- and calbindin-containing neurons in hippocampus and septum.

The median raphe nucleus is involved in controlling and maintaining hippocampal activity through its projection to inhibitory neurons in medial septum and hippocampus. It has been shown that anterogradely axonal-traced fibers originating in the median raphe nucleus project onto calbindin-containing neurons in hippocampus and parvalbumin-containing neurons in medial septum. Parallel immunohistochemistry studies showing serotonin fibers contacting calbindin- and parvalbumin-positive neurons have led to the assumption that raphe fibers projecting on these types of neurons are mainly serotonergic. However, in both dorsal and median raphe nucleus there is a large amount of non-serotonergic neurons which also are projecting neurons, indicating that a part of the raphe fibers projecting to hippocampus and septum may be non-serotonergic. Our aim was to determine whether there is a non-serotonergic projection from the raphe nucleus onto calbindin- and parvalbumin-containing neurons in hippocampus and septum. Biotin dextran amine was used as the anterograde neuronal tracer and injected into either dorsal or median raphe nucleus. By use of triple immunofluorescence-labeling we analyzed the serotonergic content of the biotin dextran amine-labeled fibers contacting parvalbumin- and calbindin-positive neurons. Surprisingly, we found a significant non-serotonergic projection from both dorsal and median raphe nuclei onto calbindin- and parvalbumin-containing interneurons in septum and hippocampus, with a preference in hippocampus for projecting onto calbindin-positive neurons. These results indicate that the raphe nuclei may exert their control on hippocampal and septal activity not only through a serotonergic projection, but also through a significant non-serotonergic pathway.

Animals↗

PubMed2001

Serotonin induces a decrease of 5-HT(1A) immunoreactivity in organotypic hippocampal cultures.

Serotonin reuptake inhibitors used for the treatment of depression act by increasing serotonin levels at the synaptic cleft and thereby activating 5-HT(1A) serotonin receptors. However, the effect of increased levels of serotonin on postsynaptic 5-HT(1A) receptor density is unknown. The purpose of this study was to investigate, in a culture model, how postsynaptic 5-HT(1A) receptors are influenced by serotonin. Different concentrations of serotonin (0.5, 1, 10, 50 and 100 microM) were added to organotypic hippocampal cultures and incubated for 1 week. The cultures were immunostained for the 5-HT(1A) receptor and the staining analyzed densitometrically. 5-HT(1A) levels decreased with increasing serotonin concentrations, being significant at 10, 50 and 100 microM. These results indicate that at increasing serotonin levels the density of postsynaptic 5-HT(1A) receptors is down-regulated.

Animals↗

PubMed2001

Rho signals to cell growth and apoptosis.

Ras and Rho GTPases are among the best studied signaling molecules in molecular biology. Essential cellular processes, such as cell growth, lipid metabolism, cytoarchitecture, membrane trafficking, transcriptional regulation, apoptosis, and response to genotoxic agents, are directly modulated by different members of this superfamily of proteins. Not until recently have we begun to understand the physiological implications of Ras and Rho GTPases, linking them to processes such as embryonic development, tissue remodeling, tumorigenesis and metastasis. In this sense, uncontrolled activation, due to overexpression of different members of the Rho family in a variety of tissues, leads to uncontrolled proliferation and invasiveness of human tumors. In this review, an attempt to briefly integrate recent findings in transcriptional regulation by Rho GTPases in the context of carcinogenesis and metastasis as well as apoptosis is made.

Animals↗

PubMed2001

Factors associated with physical activity among Spanish youth through the National Health Survey.

BACKGROUND: Physical inactivity is emerging as one of the largest public health problems throughout Europe. This study updates descriptive data on physical activity and the factors associated with it among the 6- to 15-year-old Spanish population during leisure time through the National Health Survey. METHODS: This is a cross-sectional study from a representative sample of Spanish children's physical activity during their leisure time. Sample size was 1,358 children between the ages of 6 and 15 years. Univariate analyses were carried out first, and then significant variables were entered into a logistical regression nonconditional model. RESULTS: Less than 30% of children were active and the percentage of active boys was higher than that of active girls in all age categories. From the age of 11 the percentage of total active children was stabilized. Children from the two highest social statuses (SS) were significantly more active than children from the lowest SS group. Children from large towns were more active than children from small towns. Active children reported eating more meat or fish than the less active ones. CONCLUSIONS: The results suggest that characteristics of age, sex, town size, and social status should be considered when designing physical activity strategies for Spanish children.

Adolescent↗

PubMed2001

Searching new targets for anticancer drug design: the families of Ras and Rho GTPases and their effectors.

The Ras superfamily of low-molecular-weight GTPases are proteins that, in response to diverse stimuli, control key cellular processes such as cell growth and development, apoptosis, lipid metabolism, cytoarchitecture, membrane trafficking, and transcriptional regulation. More than 100 genes of this superfamily grouped in six subfamilies have been described so far, pointing to the complexities and specificities of their cellular functions. Dysregulation of members of at least two of these families (the Ras and the Rho families) is involved in the events that lead to the uncontrolled proliferation and invasiveness of human tumors. In recent years, the cloning and characterization of downstream effectors for Ras and Rho proteins have given crucial clues to the specific pathways that lead to aberrant cellular growth and ultimately to tumorigenesis. A direct link between the functions of some of these effectors with the appearance of transformed cells and their ability to proliferate and invade surrounding tissues has been made. Accordingly, drugs that specifically alter their functions display antineoplasic properties, and some of these drugs are already under clinical trials. In this review, we survey the progress made in understanding the underlying molecular connections between carcinogenesis and the specific cellular functions elicited by some of these effectors. We also discuss new drugs with antineoplastic or antimetastatic activity that are targeted to specific effectors for Ras or Rho proteins.

Antineoplastic Agents↗

PubMed2001

Simultaneous tyrosine and serine phosphorylation of STAT3 transcription factor is involved in Rho A GTPase oncogenic transformation.

Stats (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that on a specific stimulus migrate to the nucleus and exert their transcriptional activity. Here we report a novel signaling pathway whereby RhoA can efficiently modulate Stat3 transcriptional activity by inducing its simultaneous tyrosine and serine phosphorylation. Tyrosine phosphorylation is exerted via a member of the Src family of kinases (SrcFK) and JAK2, whereas the JNK pathway mediates serine phosphorylation. Furthermore, cooperation of both tyrosine as well as serine phosphorylation is necessary for full activation of Stat3. Induction of Stat3 activity depends on the effector domain of RhoA and correlates with induction of both Src Kinase-related and JNK activities. Activation of Stat3 has biological implications. Coexpression of an oncogenic version of RhoA along with the wild-type, nontransforming Stat3 gene, significantly enhances its oncogenic activity on human HEK cells, suggesting that Stat3 is an essential component of RhoA-mediated transformation. In keeping with this, dominant negative Stat3 mutants or inhibition of its tyrosine or serine phosphorylation completely abrogate RhoA oncogenic potential. Taken together, these results indicate that Stat3 is an important player in RhoA-mediated oncogenic transformation, which requires simultaneous phosphorylation at both tyrosine and serine residues by specific signaling events triggered by RhoA effectors.

Animals↗

PubMed2000

Apoptosis induced by Rac GTPase correlates with induction of FasL and ceramides production.

Rho proteins, members of the Ras superfamily of GTPases, are critical elements in signal transduction pathways governing cell proliferation and cell death. Different members of the family of human Rho GTPases, including RhoA, RhoC, and Rac1, participate in the regulation of apoptosis in response to cytokines and serum deprivation in different cell systems. Here, we have characterized the mechanism of apoptosis induced by Rac1 in NIH 3T3 cells. It requires protein synthesis and caspase-3 activity, but it is independent of the release of cytochrome c from mitochondria. Moreover, an increase in mitochondria membrane potential and the production of reactive oxygen species was observed. Rac1-induced apoptosis was related to the simultaneous increase in ceramide production and synthesis of FasL. Generation of FasL may be mediated by transcriptional regulation involving both c-Jun amino terminal kinase as well as nuclear factor-kappa B-dependent signals. None of these signals, ceramides or FasL, was sufficient to induce apoptosis in the parental cell line, NIH 3T3 cells. However, any of them was sufficient to induce apoptosis in the Rac1-expressing cells. Finally, inhibition of FasL signaling drastically reduced apoptosis by Rac1. Thus, Rac1 seems to induce apoptosis by a complex mechanism involving the generation of ceramides and the de novo synthesis of FasL. These results suggest that apoptosis mediated by Rac1 results from a signaling mechanism that involves biochemical and transcriptional events under control of Rac1.

3T3 Cells↗

PubMed1999

[Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population].

BACKGROUND: The revalidation of the Mini Examen Cognoscitivo (MEC), first Spanish version (1978) of the Mini-Mental Status Examination (MMSE) and documentation of "population-based norms" should clarify the potential confusion induced by later versions of MMSE. METHODS CONTEXT: The Zaragoza Study on the prevalence of dementia and depression in a representative sample of the elderly community (N = 1,080). INSTRUMENTS: MEC-35 and MEC-30 points, and validated, Spanish versions of Geriatric Mental State (GMS), History and Aetiology Schedule (HAS) and Social Status Schedule (SSS). PROCEDURE: a) validation of MEC (standardized lay interviewers) against the gold standard of psychiatric diagnosis (DSM-III-R), two months later; b) "population-based norms" in the "healthy" population, and c) comparison with other MMSE versions. RESULTS: The instrument fulfills criteria of "feasibility", "content", "procedural" and "construct validity". Test-retest reliability: weighted kappa = 0.637. MEC-30 (cut-off point 23/24), sensitivity = 89.8%, specificity = 75.1% (80.8% with the cut-off at 22/23), and ROC curve, AUC = 0.920. The coefficients of individual items were satisfactory and the specificity increases in MEC-35 (83.9%). Other MMSE Spanish versions have not improved these coefficients. "Population-based norms" confirm the hypothesized influence of age and education level. MEC-30 is the version with most comparable results with the MMSE in USA. CONCLUSIONS: The validity of MEC is confirmed in the elderly population, with the same cut-off points recommended in the original standardization. MEC-30 is the best version for international comparisons.

Age Factors↗

PubMed1998

Impaired learning correlates with size of excitotoxic hippocampal CA3 lesions in adult rats, but shows no amelioration by CA3 transplants.

Hippocampal CA3 pyramidal cells grafted as cell suspensions to excitotoxic hippocampal lesions in adult rats can exchange several types of short and long range nerve connections with the host brain. We now examined whether such grafts also had functional effects in terms of ameliorating lesion-induced learning and memory deficits. Adult, male rats with bilateral, one week old, ibotenic acid-lesions of the hippocampal CA3 region, were grafted with suspensions of fetal (E18-19) CA3 cells. Seven weeks later the animals were tested for spatial navigation in the Morris Watermaze, together with groups of lesion-only and sham-operated, control rats. The tests were performed over 5 days, with 4 trials per day. At the end of the trials, the size of the lesions and the size and structural incorporation of the transplants in the host brains were evaluated morphometrically for correlations with the behavioural data. We found significant differences in swim pathlength and latency to find the platform in the Morris Watermaze between the lesion-only group and the grafted group versus the sham operated group, but no significant difference between the lesion-only and the grafted group. There was a significant positive correlation between the size of the CA3 lesions and the paucity of performance of the rat in the Watermaze, just as spontaneous recovery accordingly had not occurred over the 8 weeks postlesion. We conclude that the behavioural improvement exerted by the CA3 cell suspension grafts, at a time point when graft-host connections have had time to establish, is at most incomplete by these transplants, pointing to the difficulties there may be in obtaining full functional integration.

Journal Article↗

PubMed1995

c-JUN, KROX-24, and c-FOS expression in hippocampal grafts placed in excitotoxic hippocampal lesions of the rat.

Hippocampal transplants were examined for the expression of three specific immediate early gene encoded proteins in order to establish if grafted immature tissue maintains the basic molecular program necessary for gene transcription after grafting to excitotoxic (ibotenic acid-induced) lesions in adult host rat brains. The transplants were derived from newborn donor rats and were analyzed immunocytochemically for the presence of c-JUN, KROX-24, and c-FOS transcription factors 5 months after grafting. The expression and distribution patterns of these genes in the host hippocampus were identical to those in hippocampal neurons of normal untreated animals. c-JUN-, KROX-24-, and c-FOS-labeled neurons were also present in the transplants, where KROX-24 and c-FOS exhibited a distribution similar to host hippocampus. In contrast, c-JUN was more extensively expressed in the transplants, suggesting a molecular response to the grafting conditions and the actual graft-host brain interactions.

Animals↗

PubMedDate not supplied

Comparison of two low-calorie diets: a prospective study of effectiveness and safety.

OBJECTIVE: To evaluate the cost-effectiveness and safety of two distinct low calorie diets (LCD). DESIGN: Prospective controlled study. METHODS: 67 obese patients [body mass index (BMI) 40 kg/m2] were included in two study groups. Group A: 26 patients followed a 458 kcal diet given in three meals for 1 month. Group B: 41 patients followed a 800 kcal diet for 3 months and with outpatient control. MEASUREMENTS: Anthropometric, cardiovascular risk and nutritional profile changes were evaluated, as well as total direct and indirect costs, and the incidence of complications. RESULTS: No significant initial differences were observed between the two study groups. Eighty-six point two per cent of the patients completed the therapy correctly. After treatment a significant decrease was observed in the following variables for both groups, but no differences were detected between Groups A and B: mean weight loss (A= 9.28 kg, B= 8.7 kg), ponderal loss percentage (A/B= 7.2/6.8%), glycemia (A/B= 18.6/12.1 mg/dl), systolic blood pressure (SBP) (A/B= 11.8/6.5 mmHg), diastolic blood pressure (DBP) (A/B 5.9/6.8 mmHg), and final insulin-resistance (IR) index (A= 4.4, B= 4.3). Group A had the highest drop in total cholesterol (37.7 vs 8.1 mg/dl) and triglycerides (54.4 vs 2.5 mg/dl). No changes were observed in ureic acid, renal function and serum albumin. Thirty-six patients (55.3%) suffered trivial complications associated to the VLCD (16.9% gastrointestinal, 20% anxiety), with no differences between groups. Group A patients were on sick leave due to asthenia, and two patients in this group had serious complications (transient ischemic attack and atrial fibrillation). The total cost of Group A treatment was 3018.9 against 582.6 euros for Group B. CONCLUSIONS: The 3-month 800 kcal/day VLCD was more cost-effective and safer than the 1-month 458 kcal/day diet.

Adult↗

PubMedDate not supplied

[Prognostic morbidity and mortality factors in hospital enteral nutrition: prospective study].

OBJECTIVE: To determine the prognostic factors that may best for see the outcome of an enteral nutritional intervention and to assess the assistance quality of a nutrition unit. SETTING AND SUBJECTS: Patients that required enteral nutrition during hospital admission at a third level center. INTERVENTIONS: Observational prospective study in which 160 patients were included by means of consecutive sampling, for a 6-months follow-up period. Underlying pathology, disability degree, nutritional assessment, type of enteral nutrition, complications, nursing care, and clinical course of patients were determined. RESULTS: severe caloric and protein hyponutrition was diagnosed in 48.4 and 52.9% of patients; stress degree was moderate in 52.2% and severe in 36.5%. In 88.2% of patients variation of protein parameters was unchanged or improved, with a 0.26 g/dL increase in albumin levels and 2.4 m/dL in prealbumin (p < 0.05). Multivariate analysis adjusted for plasma albumin at admission showed that besides this biochemical parameter, a severe stress degree, a decreased alertness level, and worsening of protein variation during admission are independent prognostic mortality factors during an enteral nutritional intervention in the hospitalized patient (p < 0.05). CONCLUSIONS: alertness level, degree of caloric hyponutrition, stress degree, plasma albumin levels, and variation of protein parameters during nutritional support are independent prognostic factors for the nutritional intervention outcomes. The development of global monitoring systems of assistance activity and quality of Nutrition Units is paramount in order to improve the efficiency of enteral nutritional support at the hospital setting, to advance in patients care and promote the development of nutritional therapy.

Enteral Nutrition↗