Biomedical subjects

S Moreno

Publications and source records attributed to S Moreno.

At least 19 recordsLinked to original sources

PubMed2006

Mucor rouxii ultrastructure: cyclic AMP and actin cytoskeleton.

A comparative analysis of the effect of two compounds, dibutyryl-cyclic-AMP (dbcAMP) and latrunculin B, on the morphology and ultrastructure of the dimorphic fungus Mucor rouxii under aerobic growth conditions is presented. dbcAMP acts through the sustained activation of protein kinase A, and latrunculin B through the disruption of the actin cytoskeleton. Upon addition of these compounds to the growth medium at any stage of the germination process, cells lost polarised growth and switched to isodiametric growth. The effect was reversible. The morphologies, visualised by light microscopy or scanning electron microscopy (SEM), were alike. A switch from a rough to a smooth surface was observed by SEM when cells were repolarised by removal of the added compound. Ultrastructural changes under both conditions, as observed by transmission electron microscopy, were similar, the main feature being the enlargement of the cell wall, with irregular depositions, and detachment from the cell membrane. dbcAMP-treated cells showed a decrease in the number of glycogen granules compared with control and latrunculin B-treated cells. F-actin staining with fluorescein isothiocyanate-phalloidin showed that both dbcAMP- and latrunculin B-treated cells displayed a much lower fluorescence than control cells, with only a few pale plaques. The results suggest that the sustained activation of protein kinase A, which impairs polarised growth, might exert its effect through a modification of actin cytoskeleton organisation, very probably also involving an integrinlike pathway, as judged by the cell wall detachment and loss of cell adhesiveness of the dbcAMP-treated isodiametric cells.

Actins↗

PubMed2006

Treatment of long-term intravascular catheter-related bacteraemia with antibiotic-lock therapy.

BACKGROUND: Bacteraemia is a major complication associated with the use of long-term intravascular catheters. Conservative treatment using antibiotic-lock therapy (ALT) has been shown to be useful in some studies, but the evidence supporting its impact in clinical care is still scarce. METHODS: We evaluated the outcome of the episodes of catheter-related bacteraemia (CRB) associated with long-term intravascular devices used for chemotherapy or parenteral nutrition and that were managed with ALT during a 44 month period in our hospital. Episodes of CRB associated with catheters implanted in the same department during the same period, and that were managed with only systemic antibiotics were used as a control group. Antibiotic-lock solution consisted of a heparin solution of 20 IU/mL including vancomycin (for Gram-positive microorganisms) or ciprofloxacin or gentamicin (for Gram-negative bacilli), all at a concentration of 2 mg/mL. ALT was used for a minimum of 8-12 h/day, during 5-14 days. Effectiveness was assessed by clinical and microbiological criteria. RESULTS: A total of 801 long-term intravascular devices were placed in 105 patients during this period. There were 127 episodes of bacteraemia documented in these patients, with 92 being CRB. Of these, 48 episodes fulfilled inclusion criteria for the analysis. Nineteen episodes were treated with ALT plus systemic antibiotics, and 29 episodes were treated only with systemic antibiotics. Isolated microorganisms were similar in the two groups. The catheter had to be removed during therapy in one episode in the antibiotic-lock group and in seven episodes in the control group. Relapse of the bacteraemia with the same microorganism after stopping therapy was observed in two and three patients in the study group and the control group, respectively. Overall, successful treatment was achieved in 84% and 65% of the episodes in the antibiotic-lock group and the control group, respectively (P = 0.27). CONCLUSIONS: ALT appears as an effective conservative treatment in the management of CRB associated with long-term intravascular devices (84% in the present series), especially in infections caused by coagulase-negative staphylococci.

Anti-Bacterial Agents↗

PubMed2006

Prevalence of HIV-1 drug resistance mutations among Spanish prison inmates.

The aim of this cross-sectional study was to analyse the prevalence of HIV-1 drug-resistance mutations among HIV-1-infected prison inmates in Spain. Treatment-naive and treatment-experienced patients with an HIV RNA viral load of >/=2,000 copies/ml were included. To ensure that the study population was representative of the entire HIV-infected Spanish inmate population, a two-stage conglomerate for selection of the sample was used. In the first stage, 15 prisons were randomly selected, and in the second stage, 38 patients (30 treatment-experienced and 8 treatment-naive) per centre were randomly selected. Genotyping was performed by automatic sequencing. Resistance testing was performed on viral strains from 184 inmates from 12 prisons. Valid sequences were obtained from 133 inmates (90 treatment-experienced and 43 treatment-naive inmates). Most (92.5%) were men and had acquired HIV infection by intravenous drug use (91%); their mean age was 35 years. One or more key resistance mutations were detected in 5 (11.6%) treatment-naive and in 35 (38.6%) treatment-experienced patients. Among treatment-naive and treatment-experienced patients, resistance to nucleoside reverse transcriptase inhibitors was found in 3 (6.9%) and in 20 (22.2%) patients, respectively, resistance to non-nucleoside reverse transcriptase inhibitors in 3 (6.9%) and in 21 (23.3%) patients, and resistance to protease inhibitors in 3 (6.9%) and in 14 (15.5%) patients. Multidrug resistance was detected in 1 of the 43 (2.3%) treatment-naive patients. These findings support the use of resistance testing in HIV-infected inmates who must begin antiretroviral therapy, given the high rate of primary resistance to drugs frequently included in the initial treatment regimens.

Adult↗

PubMed2006

Feminizing adreno-cortical carcinomas in male adults. A dire prognosis. Three cases in a series of 801 adrenalectomies and review of the literature.

UNLABELLED: We describe the clinical presentation, biochemical features, diagnostic criteria, clinical course and differential diagnosis in three cases of feminizing adreno-cortical carcinoma (FACC) with a review of the literature. PATIENTS: From 1970 throughout December 2003 among a series of 801 adrenalectomies, three had been performed for FACC. RESULTS: Age at presentation was 74, 63 and 23 years. Estradiol hypersecretion was observed in 3/3 patients, 17 OH progesterone was elevated in 2/3 patients and both of them had a diminution of testosterone, delta 4 androstenedione was elevated in 1/3 patients. Imaging studies suggested malignancy in 3/3 patients by the presence of necrosis, heterogeneity, calcifications, size of the tumor and compression of adjacent organs. All patients were stage III at presentation and had a Weiss score >or=6. Size and weight of the tumors were 30, 20, 15cm and 3750, 480 and 275g respectively. All 3 patients received mitotane and cortisone post-operatively and at follow up (7, 3 and 2 years) all 3 died of the disease. CONCLUSIONS: Feminizing adreno-cortical carcinomas in adults are exceedingly rare (1-2% of adreno-cortical carcinomas). Tumors are huge and even after surgery for cure their prognosis is worse than for other varieties of adreno-cortical carcinomas either secreting or non secreting. Early diagnosis and treatment may improve overall prognosis.

Adrenal Cortex Neoplasms↗

PubMed2006

Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus.

To evaluate, among 70 hepatitis C virus (HCV)-monoinfected and 36 human immunodeficiency virus (HIV)-coinfected naïve patients with genotypes 1/4 receiving weight-adjusted pegylated interferon-alpha-2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV-RNA decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut-off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV-RNA (5.75 vs 5.72 log(10)IU/ml, P = 0.6), HCV monoinfection led to significantly lower HCV-RNA values at weeks 4 (3.7 vs 4.3 log(10)IU/ml, P = 0.01), 12 (2.3 vs 3.5 log(10)IU/ml, P = 0.01) and 24 (1.4 vs 3.3 log(10)IU/ml, P = 0.001) and a higher rates of viral clearance at weeks 24 (60%vs 36%, P = 0.02), 48 (46%vs 25%, P = 0.03) and 72 (37%vs 17%). The lack of achieving an HCV-RNA decrease of at least 1 log(10) at week 4 was highly predictive of treatment failure for HCV-monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0.86 [95% confidence interval (CI) 0.77-0.95], but not for HCV/HIV-coinfected patients (cut-off, 0 log(10), Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0.71 (95% CI 0.49-0.93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1.08-8.04, P = 0.01). Thus the magnitude of HCV-RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.

Adult↗

PubMed2005

Once-daily antiretroviral therapy: Spanish Consensus Statement.

BACKGROUND: Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use. OBJECTIVES: This document examines the characteristics and possibilities of treatment administered once daily. METHODS: Consensus of 248 Spanish experts in the field. RESULTS: Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy. CONCLUSIONS: Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.

Anti-HIV Agents↗

PubMed2005

Reactivation of hepatitis B in an HIV-infected patient with antibodies against hepatitis B core antigen as the only serological marker.

Presented here is the first report of clinical reactivation of hepatitis B virus (HBV) in an HIV-infected patient who previously had anti-HBc as the only serological marker of past infection (anti-HBc alone). Reactivation occurred after lamivudine was removed from the patient's antiretroviral treatment regimen due to lack of virological response. HIV-infected patients frequently present anti-HBc alone, and in some cases this serological profile is associated with occult HBV infection. The current case demonstrates the importance of ruling out the possibility of occult infection in this patient group.

Adult↗

PubMed2005

Peroxisome proliferator-activated receptors (PPARs) and related transcription factors in differentiating astrocyte cultures.

Peroxisome proliferator-activated receptors (PPARs), retinoid X receptors (RXRs), CCAAT/enhancer binding proteins (C/EBPs) and beta-catenin are transcription factors involved in cell differentiation. The aim of this work was to investigate the occurrence and variations of these proteins during astrocyte differentiation. Primary cultures of mouse cortical astrocytes were characterized using nestin, A2B5 and glial fibrillary acidic protein (GFAP) as differentiation markers, during a period of 21 days in vitro (DIV). Glycogen and triglyceride accumulation were also studied. At 3 DIV the cultures were mainly constituted by neural progenitor cells, as assessed by their immunofluorescent pattern. At this time PPARs and beta-catenin were localized to the cytoplasm. Interestingly, some cells contained Oil Red O-positive lipid droplets. Between 7 and 21 DIV, nestin decreased, while GFAP increased, indicating ongoing astroglial differentiation. beta-catenin, predominantly nuclear at 7 DIV, later localized to membranes. Redistribution of all three PPAR isotypes from the cytoplasm to the nucleus was observed starting from 7 DIV. Between 7 and 14 DIV, C/EBPalpha, PPARalpha, RXRalpha and glycogen content increased. Between 14 and 21 DIV, PPARbeta/delta decreased, while PPARgamma, C/EBPbeta and delta and lipid droplet-containing cells increased. At 21 DIV both A2B5-/GFAP+ and A2B5+/GFAP+ cells were predominantly observed, indicating differentiation toward type-1 and type-2 astrocytes, although the presence of GFAP- cells demonstrates the persistence of neural precursors in the culture even at this time point. In conclusion, our results, reporting modifications of PPARs, RXRs, C/EBPs and beta-catenin during culture time, strongly suggest the involvement of these transcription factors in astrocyte differentiation. Specifically, beta-catenin translocation from the nucleus to plasma membrane, together with PPARbeta/delta decrease and C/EBPalpha increase, could be related to decreased proliferation at confluence, while PPARalpha and gamma and all C/EBPs could participate in differentiation processes, such as glycogenesis and lipidogenesis.

Animals↗

PubMed2005

Catalytic wet peroxide oxidation of phenol by pillared clays containing Al-Ce-Fe.

A Colombian bentonite was successfully pillared with mixed polyhydroxocationic solutions of Al-Fe or Al-Ce-Fe, with the iron in small quantities, to generate a modified Fenton process on the surface of the pillared clays with a possible activation of the hydrogen peroxide and the organic substances on the iron sites of the solids in order to obtain active and stable catalysts for the wet peroxide oxidation of organic pollutants from industrial wastewaters. The catalysts were very efficient in the reaction of phenol oxidation in diluted aqueous media under mild experimental conditions (298 K and atmospheric pressure) and in the elimination of the different intermediary compounds of the reaction reaching high-mineralization levels. The solids showed high stability in the reaction media due to the strong interaction between the iron species and the catalyst support. The incorporation of Ce in the solids showed a favorable effect in the pillaring of the materials allowing the increase of the basal spacing and enhancing the catalytic activity of the solids.

Aluminum↗

PubMed2005

The effect of calcium channel blockers on outcome following the surgical treatment of phaeochromocytomas and paragangliomas.

The peri-operative management of patients undergoing surgery for phaeochromocytoma or paraganglioma with calcium channel blockers (CCB) and their impact on postoperative morbidity and mortality were studied. The medical records of 105 patients undergoing surgery between 1991 and 2002 were analysed retrospectively. In all patients, the calcium channel blocker nicardipine was used for the peri-operative management of haemodynamic changes. Sixty-five patients (61.9%) showed transient intra-operative hypertension. Systolic blood pressure (SBP) > 220 mmHg and SBP > 180 mmHg for > 10 consecutive minutes was observed in 14 (13%) and four patients (2.8%), respectively. SBP < 80 mmHg for > 10 consecutive minutes occurred in 13 patients (12.3%). Eleven patients (10.4%) developed postoperative complications and three patients died (2.8%). The median (range) ICU and hospital length of stay were, respectively, 1 (0-7) day and 10 (2-35) days. The sole use of calcium channel blockers for the peri-operative management of phaeochromocytoma and paraganglioma resection does not prevent all haemodynamic changes; however, its use was associated with a low morbidity and mortality.

Adolescent↗

PubMed2005

Nosocomial bloodstream infections caused by Streptococcus pneumoniae.

A retrospective study of Streptococcus pneumoniae bacteraemia among adult patients in two large teaching hospitals in Spain identified 108 (10.6%) of 1,020 episodes as nosocomial pneumococcal bloodstream infections (NPBIs). Seventy-seven clinical records with sufficient data were available for analysis. The interval between admission and a positive blood culture was 3--135 days (median 17 days; interquartile range 8--27). The main underlying and predisposing conditions for NPBI were malignancy (31%), chronic obstructive pulmonary disease (28.6%), heart failure (16.9%), chronic renal failure (15.6%), liver cirrhosis (13%) and infection with human immunodeficiency virus (13%). Overall, 31.2% of patients developed severe sepsis, 11.7% septic shock, and 3.9% multi-organ failure. The main portals of entry were pneumonia (70.1%), meningitis (5.2%) and primary peritonitis (5.2%). Of the responsible serogroups, 78% were included in the 23-valent polysaccharide vaccine. Thirty-five (45.5%) patients died, with death considered to be related to the NPBI in 21 (27.3%) cases. Following multivariate analysis, factors that independently predicted death after adjusting for age were: ultimately fatal underlying disease (OR, 8.9; 95% CI, 0.8--94.3; p<0.001); rapidly fatal underlying disease (OR, 15.0; 95% CI, 2.8--81.3; p<0.001); heart failure (OR, 8.11; 95% CI, 1.1--60.8; p<0.03); inadequate empirical therapy (OR, 10.6; 95% CI, 1.2--97; p<0.003); a severe sepsis score (OR, 9.5; 95% CI, 1.9--47.0; p<0.001); and septic shock or multi-organ failure (OR, 63.7; 95% CI, 4.9--820.7; p<0.001). Adequate empirical therapy was an independent protective factor (OR, 0.05; 95% CI, 0.04--0.58; p<0.005), but the use of more than one antimicrobial agent was not.

Adult↗

PubMed2005

Incidence and mutation rates of Huntington's disease in Spain: experience of 9 years of direct genetic testing.

BACKGROUND: Prior to the discovery of the Huntington's disease (HD) mutation, the prevalence, incidence, and new mutation rates for this disease were based on the presence of progressive choreic movements and a positive family history. OBJECTIVE: To evaluate the uptake of the HD genetic analysis in Spain, and to provide additional information on the epidemiology of this disease from the experience of 9 years of direct genetic testing. METHODS: From 1994 to 2002, CAG repeat length was determined in 317 patients with symptoms compatible with HD. In all cases, demographic, clinical, and family data were carefully reviewed. RESULTS: HD diagnosis (CAG repeat length >/=36) was confirmed in 166 (52%) symptomatic cases. Of these, 76 (45.8%) reported a positive family history and in 21 cases (12.7%) family history was negative. New mutation events were genetically proven in three families and highly suspected in another, estimating that the minimum new mutation rate for HD in our population is >4%, with a potential mutation rate of 8%. More than 16% of all HD cases had late onset (>59 years) of symptoms, and in three quarters of these the family history was negative. The incidence rate for the autonomous communities of Navarra and the Basque country, based on the number of newly diagnosed cases by genetic testing, was 4.7 per million per year. CONCLUSIONS: Direct HD genetic testing shows that the incidence and mutation rates of the disease are 2-3 times higher than previously reported. We also demonstrated the relevance of CAG repeat length assessment in diagnosing patients with late onset of symptoms and negative family history for HD.

Adolescent↗

PubMed2005

Sacral myeloradiculitis complicating genital herpes in a HIV-infected patient.

Myeloradiculitis is a rare neurological complication of herpes simplex type 2 (HSV-2) infection, frequently associated with a fatal outcome. Among patients with HIV infection, HSV-2 myeloradiculitis has occasionally been reported, always associated with advanced immunosuppression and AIDS. We report a patient with HIV infection but no history of previous opportunistic infections, who developed sacral myeloradiculitis immediately after an episode of genital herpes. Magnetic resonance imaging with gadolinium showed necrotizing myelitis in the conus medullaris and enhancement of sacral roots. CD4 lymphocyte count was 530/mm3. Other possible causes of myeloradiculitis in HIV-infected patients were appropriately excluded. Acyclovir therapy resulted in partial clinical improvement. This report shows that myeloradiculitis as a complication of genital herpes may occur in the early stages of HIV infection and may have a favourable outcome with antiviral treatment.

Adult↗

PubMed2004

Analysis of a quantitative PCR assay for CMV infection in liver transplant recipients: an intent to find the optimal cut-off value.

BACKGROUND: Preemptive therapy required highly predictive tests for CMV disease. CMV antigenemia assay (pp65 Ag) has been commonly used for rapid diagnosis of CMV infection. Amplification methods for early detection of CMV DNA are under analysis. OBJECTIVES: To compare two diagnostic methods for CMV infection and disease in this population: quantitative PCR (qPCR) performed in two different samples, plasma and leukocytes (PMNs) and using a commercial diagnostic test (COBAS Amplicor Monitor Test) versus pp65 Ag. STUDY DESIGN: Prospective study conducted in liver transplant recipients from February 2000 to February 2001. RESULTS: Analyses were performed on 164 samples collected weekly during early post-transplant period from 33 patients. Agreements higher than 78% were observed between the three assays. Optimal qPCR cut-off values were calculated using ROC curves for two specific antigenemia values. For antigenemia >or=10 positive cells, the optimal cut-off value for qPCR in plasma was 1330 copies/ml, with a sensitivity (S) of 58% and a specificity (E) of 98% and the optimal cut-off value for qPCR-cells was 713 copies/5x10(6) cells (S:91.7% and E:86%). Using a threshold of antigenemia >or=20 positive cells, the optimal cut-off values were 1330 copies/ml for qPCR-plasma (S 87%; E 98%) and 4755 copies/5x10(6) cells for qPCR-cells (S 87.5%; E 98%). Prediction values for the three assays were calculated in patients with CMV disease (9 pts; 27%). Considering the assays in a qualitative way, the most sensitive was CMV PCR in cells (S: 100%, E: 54%, PPV: 40%; NPV: 100%). Using specific cut-off values for disease detection the sensitivity, specificity, PPV and NPV for antigenemia >or=10 positive cells were: 89%; 83%; 67%; 95%, respectively. For qPCR-cells >or=713 copies/5x10(6) cells: 100%; 54%; 33% and 100% and for plasma-qPCR>or=1330 copies/ml: 78%, 77%, 47%, 89% respectively. CONCLUSIONS: Optimal cut-off for viral load performed in plasma and cells can be obtained for the breakpoint antigenemia value recommended for initiating preemptive therapy with high specificities and sensitivities. Diagnostic assays like CMV pp65 Ag and quantitative PCR for CMV have similar efficiency and could be recommended as methods of choice for diagnosis and monitoring of active CMV infection after transplantation.

Antigens, Viral↗

PubMed2004

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

AIDS Vaccines↗

PubMed2004

Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis.

Adenosine deaminase activity (ADA) determination in cerebrospinal fluid (CSF) is considered a specific test for the diagnosis of tuberculous meningitis. In order to study the variability of this marker in patients with different neurological disorders associated with HIV infection, and its utility for the diagnosis of tuberculous meningitis in these patients, the ADA levels in 417 CSF samples from HIV-infected patients with neurological symptoms were reviewed. HIV infection, HIV-associated neurological disorders, and progressive multifocal leukoencephalopathy were not associated with elevated ADA in CSF. Among patients with meningitis, receiver operating characteristic curve analysis gave an optimal ADA cut-off point of 8.5 IU/l for the diagnosis of tuberculous meningitis, with 57% sensitivity, 87% specificity, and an area under the curve of 0.747 (similar to that for CSF glucose concentration). False-positive results were found in patients with neurological CMV disease and cryptococcal, lymphomatous, and probable candidal meningitis. The results of this study indicate that ADA determination in CSF has limited utility for the diagnosis of tuberculous meningitis in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

PubMed2004

DNA immunisation with minimalistic expression constructs.

The low efficacy obtained in large animals makes plasmid-based DNA vaccines commercially unviable. Another concern is the presence of antibiotic resistance markers on virtually all conventional plasmids. Here we describe the use of minimalistic, immunogenically defined gene expression (MIDGE) vectors for DNA vaccination. MIDGE are linear, covalently-closed vectors containing all the essential information for gene expression and none of the non-essential and potentially dangerous plasmid backbone sequences. MIDGE vectors can also be chemically modified on both ends at defined positions allowing targeting of the DNA to specific cell types or cellular compartments. Immunisation of mice with simple and end-modified MIDGE vectors showed that they are efficacious tools to generate and/or manipulate antigen-specific immune responses.

Animals↗

PubMed2004

Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS.

Peroxisome proliferator-activated and retinoid X receptors (PPARs and RXRs) are transcription factors belonging to the steroid hormone receptor superfamily. Upon activation by their ligands, PPARs and RXRs bind to their target genes as heterodimers. Ligands of these receptors include lipophylic molecules, such as retinoids, fatty acids and eicosanoids, the importance of which in the metabolism and functioning of the nervous tissue is well documented. The immunohistochemical distribution of PPARs and RXRs in the CNS of the adult rat was studied by means of a sensitive biotinyl-tyramide method. All PPAR (alpha, beta/delta and gamma) and RXR (alpha, beta and gamma) isotypes were detected and found to exhibit specific patterns of localization in the different areas of the brain and spinal cord. The presence of the nuclear receptors was observed in both neuronal and glial cells. While PPAR beta/delta and RXR beta showed a widespread distribution, alpha and gamma isotypes exhibited a more restricted pattern of expression. The frontal cortex, basal ganglia, reticular formation, some cranial nerve nuclei, deep cerebellar nuclei, and cerebellar Golgi cells appeared rather rich in all studied receptors. Based on our data, we suggest that in the adult CNS, PPARs and RXRs, besides playing roles common to many other tissues, may have specific functions in regulating the expression of genes involved in neurotransmission, and therefore play roles in complex processes, such as aging, neurodegeneration, learning and memory.

Animals↗