The mid-secretory endometrial transcriptomic landscape in endometriosis: a meta-analysis.

STUDY QUESTION: Do women with endometriosis have a different endometrial gene expression profile at the time of embryo implantation than women without endometriosis? SUMMARY ANSWER: The endometrial gene expression profile of women with endometriosis differs from that of women without endometriosis at the mid-secretory phase, although the differences are small. WHAT IS KNOWN ALREADY: About 50% of women with endometriosis suffer infertility. Several molecular studies have suggested impaired endometrial receptivity in women with endometriosis, while others have detected no dysregulation of endometrial receptivity. Nevertheless, the previous endometrial transcriptome studies comparing women with and without endometriosis have been performed in small sample size with limited statistical power. We set out to systematically search and compile data of endometrial gene expression signatures at the receptive phase in women with endometriosis versus control women. Based on the obtained data, we conducted a meta-analysis of differentially expressed genes in order to raise the power of the analysis for identifying the molecular profiles of receptive phase endometria in endometriosis. STUDY DESIGN SIZE DURATION: A systematic literature search was conducted up to February 2022 following PRISMA criteria and included PubMed, Cochrane and Web of Science databases. For the systematic search, the term 'endometriosis' was paired with the terms 'transcriptomics', 'transcriptome', 'gene expression', 'RNA-seq', 'sequencing' and 'array', by using the Boolean operator 'AND' to connect them. Articles written in English were screened and interrogated for data extraction. PARTICIPANTS/MATERIALS SETTING METHODS: A meta-analysis was performed on the selected studies to extract the differentially expressed genes described at the mid-secretory phase in women with endometriosis versus women without endometriosis in natural cycles, using the robust rank aggregation method. In total, transcriptome data of 125 women (78 patients and 47 controls) were meta-analysed, with a special focus on endometrial receptivity-specific genes based on commercial endometrial receptivity tests. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 8 studies were eligible for the quantitative meta-analysis, gathering transcriptome data from the mid-secretory phase endometria of 125 women. A total of 7779 differentially expressed transcripts between the study groups were retrieved (3496 up-regulated and 4283 down-regulated) and were meta-analysed. After stringent multiple correction, there was no differential expression of any single molecule in the endometrium of women with endometriosis versus controls, while enrichment analysis detected that the pathways of chemotaxis and locomotion are dysregulated in endometriosis. Further analysis of endometrial receptivity-specific genes highlighted dysregulation of C4BPA, MAOA and PAEP and enrichment of immune and defence pathways in women with endometriosis. LIMITATIONS REASONS FOR CAUTION: Most of the studies included into the meta-analysis were relatively small and had different study designs, which might have contributed to a bias. WIDER IMPLICATIONS OF THE FINDINGS: The current meta-analysis supports the hypothesis that endometrial receptivity is altered in women with endometriosis, although the changes are small. The molecules and pathways identified could serve as future biomarkers and therapeutical targets in detecting and treating endometriosis-associated infertility. STUDY FUNDING/COMPETING INTERESTS: The authors declare no competing interests. This work was supported by the Spanish Ministry of Education, Culture and Sport [grant FPU15/01193] and the Margarita Salas program for the Requalification of the Spanish University system [grant UJAR01MS]; Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526-R; Programa Operativo FEDER Andalucía (B-CTS-500-UGR18; A-CTS-614-UGR20); the Junta de Andalucía [BIO-302; and PAIDI P20_00158]; the University of Jaén [PAIUJA-EI_CTS02_2017]; the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR; the Estonian Research Council (grant PRG1076); Horizon 2020 innovation (ERIN, grant no. EU952516) of the European Commission and Enterprise Estonia (grant EU48695). TRIAL REGISTRATION NUMBER: The systematic review was registered at PROSPERO (identifier: CRD42020122054).

Fractal dimension analysis of states of consciousness and unconsciousness using transcranial magnetic stimulation.

BACKGROUND AND OBJECTIVE: Knowing whether a subject is conscious or not is a current challenge with a deep potential clinical impact. Recent theoretical considerations suggest that consciousness is linked to the complexity of distributed interactions within the corticothalamic system. The fractal dimension (FD) is a quantitative parameter that has been extensively used to analyse the complexity of structural and functional patterns of the human brain. In this study we investigate FD to assess whether it can discriminate between consciousness and different states of unconsciousness in healthy individuals. METHODS: We study 69 high-density electroencephalogram (hd-EEG) measurements after transcranial magnetic stimulation (TMS) in 18 healthy subjects progressing from wakefulness to non-rapid eye movement (NREM) sleep and sedation induced by different anaesthetic agents (xenon and propofol). We quantify the integration of thalamocortical networks by calculating the FD of a spatiotemporal voxelization obtained from the locations of all sources that are significantly activated by the perturbation (4DFD). Moreover, we study the temporal evolution of the evoked spatial distributions and compute a measure of the differentiation of the response by means of the Higuchi FD (HFD). Finally, a Fractal Dimension Index (FDI) of perturbational complexity is computed as the product of both quantities: integration FD (4DFD) and differentiation FD (HFD). RESULTS: We found that FDI is significantly lower in sleep and sedation when compared to wakefulness and provides an almost perfect intra-subject discrimination between conscious and unconscious states. CONCLUSIONS: These results support the combination of FD measures of cortical integration and cortical differentiation as a novel paradigm of tracking complex spatiotemporal dynamics in the brain that could provide further insights into the link between complexity and the brain's capacity to sustain consciousness.

A common molecular signature in ASD gene expression: following Root 66 to autism.

Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to build autism biomarkers. In this study, we conducted an integrated systems biology analysis of 9 independent gene expression experiments covering 657 autism, 9 mental retardation and developmental delay and 566 control samples to determine if a common signature exists and to test whether regulatory patterns in the brain relevant to autism can also be detected in blood. We constructed a matrix of differentially expressed genes from these experiments and used a Jaccard coefficient to create a gene-based phylogeny, validated by bootstrap. As expected, experiments and tissue types clustered together with high statistical confidence. However, we discovered a statistically significant subgrouping of 3 blood and 2 brain data sets from 3 different experiments rooted by a highly correlated regulatory pattern of 66 genes. This Root 66 appeared to be non-random and of potential etiologic relevance to autism, given their enriched roles in neurological processes key for normal brain growth and function, learning and memory, neurodegeneration, social behavior and cognition. Our results suggest that there is a detectable autism signature in the blood that may be a molecular echo of autism-related dysregulation in the brain.

A Web platform for the interactive visualization and analysis of the 3D fractal dimension of MRI data.

This study presents a Web platform (http://3dfd.ujaen.es) for computing and analyzing the 3D fractal dimension (3DFD) from volumetric data in an efficient, visual and interactive way. The Web platform is specially designed for working with magnetic resonance images (MRIs) of the brain. The program estimates the 3DFD by calculating the 3D box-counting of the entire volume of the brain, and also of its 3D skeleton. All of this is done in a graphical, fast and optimized way by using novel technologies like CUDA and WebGL. The usefulness of the Web platform presented is demonstrated by its application in a case study where an analysis and characterization of groups of 3D MR images is performed for three neurodegenerative diseases: Multiple Sclerosis, Intrauterine Growth Restriction and Alzheimer's disease. To the best of our knowledge, this is the first Web platform that allows the users to calculate, visualize, analyze and compare the 3DFD from MRI images in the cloud.

In vitro culture of mouse embryos reduces differential gene expression between inner cell mass and trophectoderm.

Differences in gene expression and imprinting have been reported, comparing in vivo versus in vitro generated preimplantation embryos. Furthermore, mouse studies have shown that placenta development is altered following in vitro culture. However, the molecular mechanisms underlying these findings are unknown. We therefore isolated trophectoderm (TE) and inner cell mass (ICM) cells from in vivo and in vitro fertilization (IVF) embryos and evaluated their transcriptome using microarrays. We found that the transcriptomes of in vitro produced ICM and TE cells showed remarkably few differences compared to ICM and TE cells of in vivo generated embryos. In vitro fertilization embryos showed a reduced number of TE cells compared to in vivo embryos. In addition, TE of IVF embryos showed significant downregulation of solute transporter genes and of genes involved in placenta formation (Eomesodermin, Socs3) or implantation (Hbegf). In summary, IVF and embryo culture significantly affects the transcriptome of ICM and TE cells.

Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis.

Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P(4)) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P(4), we compared early (6-h), intermediate (48-h), and late (14-Day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESF) from women with endometriosis (hESF(endo)) with hESF from women without endometriosis (hESF(nonendo)). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESF were isolated and treated with P(4) (1 µM) plus estradiol (E(2)) (10 nM), E(2) alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P(4) in both hESF(nonendo) and hESF(endo), although a blunted response to P(4) was observed in the latter. The normal response of hESF to P(4) involves a tightly regulated kinetic cascade involving key components in the P(4) receptor and MAPK signaling pathways that results in inhibition of E(2)-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESF(endo) early response to P(4). The abnormal response of this cell type to P(4) may contribute to compromised embryonic implantation and infertility in women with endometriosis.

UJA-3DFD: a program to compute the 3D fractal dimension from MRI data.

This work presents a computer program for computing the 3D fractal dimension (3DFD) from magnetic-resonance images of the brain. The program is based on an algorithm that calculates the 3D box counting of the entire volume of the brain, and also of its 3D skeletonization. The validity and accuracy of the software has been confirmed using solids with well-known 3DFD values. The usefulness of the program developed is demonstrated by its successful characterization of several neurodegenerative diseases.

Effect of ICSI on gene expression and development of mouse preimplantation embryos.

BACKGROUND: In vitro culture (IVC) and IVF of preimplantation mouse embryos are associated with changes in gene expression. It is however not known whether ICSI has additional effects on the transcriptome of mouse blastocysts. METHODS: We compared gene expression and development of mouse blastocysts produced by ICSI and cultured in Whitten's medium (ICSI(WM)) or KSOM medium with amino acids (ICSI(KSOMaa)) with control blastocysts flushed out of the uterus on post coital Day 3.5 (in vivo). In addition, we compared gene expression in embryos generated by IVF or ICSI using WM. Global pattern of gene expression was assessed using the Affymetrix 430 2.0 chip. RESULTS: Blastocysts from ICSI fertilization have a reduction in the number of trophoblastic and inner cell mass cells compared with embryos generated in vivo. Approximately 1000 genes are differentially expressed between ICSI blastocyst and in vivo blastocysts; proliferation, apoptosis and morphogenetic pathways are the most common pathways altered after IVC. Unexpectedly, expression of only 41 genes was significantly different between embryo cultured in suboptimal conditions (WM) or optimal conditions (KSOM(aa)). CONCLUSIONS: Our results suggest that fertilization by ICSI may play a more important role in shaping the transcriptome of the developing mouse embryo than the culture media used.

Comparative analysis of neurological disorders focuses genome-wide search for autism genes.

The behaviors of autism overlap with a diverse array of other neurological disorders, suggesting common molecular mechanisms. We conducted a large comparative analysis of the network of genes linked to autism with those of 432 other neurological diseases to circumscribe a multi-disorder subcomponent of autism. We leveraged the biological process and interaction properties of these multi-disorder autism genes to overcome the across-the-board multiple hypothesis corrections that a purely data-driven approach requires. Using prior knowledge of biological process, we identified 154 genes not previously linked to autism of which 42% were significantly differentially expressed in autistic individuals. Then, using prior knowledge from interaction networks of disorders related to autism, we uncovered 334 new genes that interact with published autism genes, of which 87% were significantly differentially regulated in autistic individuals. Our analysis provided a novel picture of autism from the perspective of related neurological disorders and suggested a model by which prior knowledge of interaction networks can inform and focus genome-scale studies of complex neurological disorders.

Ultrasonic characterization of granites obtained from industrial quarries of Extremadura (Spain).

The industry of ornamental rocks, such as granites, represents one of the most important industrial activities in the region of Extremadura, SW Spain. A detailed knowledge of the intrinsic properties of this natural stone and its environmental evolution is a required goal in order to fully characterize its quality. In this work, two independent NDT acoustic techniques have been used to measure the acoustic velocity of longitudinal waves in different prismatic granitic-samples of industrial quarries. A low-frequency transceiver set-up, based on a high-voltage BPV Steinkamp instrument and two 50 kHz probes, has been used to measure pulse travel times by ultrasonic through-transmission testing. In complementary fashion, an Erudite MK3 test equipment with an electromagnetic vibrator and two piezoelectric sensors has also been employed to measure ultrasonic velocity by means of a resonance-based method, using the same types of granite varieties. In addition, a comprehensive set of physical/mechanical properties have also been analyzed, according to Spanish regulations in force, by means of alternative methods including destructive techniques such as strength, porosity, absorption, etc. A large number of samples, representing the most important varieties of granites from quarries of Extremadura, have been analyzed using the above-mentioned procedures. Some results obtained by destructive techniques have been correlated with those found using ultrasonic techniques. Our experimental setting allowed a complementary characterization of granite samples and a thorough validation of the different techniques employed, thus providing the industry of ornamental rocks with a non-destructive tool that will facilitate a more detailed insight on the properties of the rocks under study.

[Nitric oxide in malignant astrocytes]. / El monóxido de nitrógeno en los astrocitomas malignos.

INTRODUCTION: One of the different molecules involved in the development of astrocytomas is nitric oxide (NO), a gaseous radical that, depending on the cell type and the experimental paradigm selected in the pathology, can play either a cytotoxic or a cytoprotective role. DEVELOPMENT: During the development of an astrocytoma NO acts as a tumouricidal agent, although it can also alter vascular reactivity and lead to neovascularisation, thereby contributing to the invasive capacity (aggressiveness) of the tumour. One of the mechanisms of tumoural progression consists in the protein inactivation resulting from the NO nitration of tyrosine from proteins coded for by tumour-suppressing genes, such as p53. Furthermore, in malignant astrocytes, nitrosoglutathione, a natural NO-donor, has been seen to play a role in the chemoresistance displayed against nitrosourea derivatives. The NO excreted by irradiated astrocytoma cells also appears to be involved in the resistance to the radiotherapy shown by non-irradiated cells. CONCLUSIONS: The molecular mechanisms behind the complex and paradoxical activity of NO in glioblastoma multiforme have still not been fully explained and its implications in vivo are even further from being completely understood.

El monóxido de nitrógeno en los astrocitomas malignos / Nitric oxide in malignant astrocytes

Introducción. Entre las diferentes moléculas implicadas en el desarrollo de los astrocitomas se encuentra el monóxido de nitrógeno (NO), un radical gaseoso que, según el tipo celular y el paradigma experimental seleccionado en patología, puede ejercer un papel citotóxico o citoprotector. Desarrollo. Durante el desarrollo de un astrocitoma, el NO presenta actividad tumoricida, aunque también puede alterar la reactividad vascular y conducir a la neo-vascularización; contribuye, de este modo, a la capacidad invasiva (agresividad) del tumor. Entre los mecanismos de progresión tumoral se encuentra la inactivación proteica derivada de la síntesis de NO, a través de la nitración de residuos de tirosina de las proteínas codificadas por genes supresores de tumores, como la p53. Además, también se ha detectado en los astrocitomas malignos la participación del nitrosoglutatión, un reservorio natural de NO, en la quimiorresistencia frente a los derivados de la nitrosourea, así como la implicación del NO excretado por las células irradiadas de astrocitoma en la resistencia a la radioterapia de células no irradiadas. Conclusión. Los mecanismos moleculares de la compleja y paradójica actividad del NO en el glioblastoma multiforme todavía no se han dilucidado del todo y, menos todavía, sus implicaciones in vivo

Introduction. One of the different molecules involved in the development of astrocytomas is nitric oxide (NO), a gaseous radical that, depending on the cell type and the experimental paradigm selected in the pathology, can play either a cytotoxic or a cytoprotective role. Development. During the development of an astrocytoma NO acts as a tumouricidal agent, although it can also alter vascular reactivity and lead to neovascularisation, thereby contributing to the invasive capacity (aggressiveness) of the tumour. One of the mechanisms of tumoural progression consists in the protein inactivation resulting from the NO nitration of tyrosine from proteins coded for by tumour-suppressing genes, such as p53. Furthermore, in malignant astrocytes, nitrosoglutathione, a natural NO-donor, has been seen to play a role in the chemoresistance displayed against nitrosourea derivatives. The NO excreted by irradiated astrocytoma cells also appears to be involved in the resistance to the radiotherapy shown by non-irradiated cells. Conclusions. The molecular mechanisms behind the complex and paradoxical activity of NO in glioblastoma multiforme have still not been fully explained and its implications in vivo are even further from being completely understood

Upregulation of endothelial nitric oxide synthase maintains nitric oxide production in the cerebellum of thioacetamide cirrhotic rats.

This study examines the expression and cellular distribution pattern of nitric oxide synthase (NOS) isoforms, nitrotyrosine-derived complexes, and the nitric oxide (NO) production in the cerebellum of rats with cirrhosis induced by thioacetamide (TAA). The results showed local changes in the tissue distribution pattern of the NOS isoforms and nitrated proteins in the cerebellum of these animals. Particularly, eNOS immunoreactivity in perivascular glial cells of the white matter was detected only in TAA-treated animals. In addition, although neither neuronal NOS (nNOS) nor inducible NOS (iNOS) cerebellar protein levels appeared to be affected, the endothelial NOS (eNOS) isoform significantly increased its expression, and NO production slightly augmented in TAA-treated rats. These NOS/NO changes may contribute differently to the evolution of the hepatic disease either by maintaining the guanosine monophosphate-NO signal transduction pathways and the physiological cerebellar functions or by inducing oxidative stress and cell damage. This model gives rise to the hypothesis that the upregulation of the eNOS maintains the physiological production of NO, while the iNOS is silenced and the nNOS remains unchanged. The differential NOS-distribution and expression pattern may be one of the mechanisms involved to balance cerebellar NO production in order to minimize TAA toxic injury. These data help elucidate the role of the NOS/NO system in the development and progress of hepatic encephalopathy associated with TAA cirrhosis.

Immunohistochemical localisation of neuronal nitric oxide synthase in the rainbow trout kidney.

The distribution of nitrergic nervous structures in the trout kidney was studied by peroxidase-linked ABC immunostaining procedures using a polyclonal antibody raised against the neuronal isoform of nitric oxide synthase. The nitrergic plexus reaches the kidney along the vasculature, mainly running with the postcardinal vein where nitrergic fibres, microganglia like cellular clusters and isolated neurones were detected. The atubular head-kidney only showed isolated nitrergic fibres close to the larger arteries. On the other hand, the collecting tubules, collecting ducts, large arteries and glomerular arterioles of the tubular middle and posterior trunks were innervated by nitrergic fibres even though immunoreactive neurones were also observed in close apposition to some tubular elements and large arteries. These results suggest that, according to morphofunctional differences between the fish and mammalian kidneys, nitrergic neural structures may be involved in the control of particular renal functions in the rainbow trout.

Neuronal nitric oxide synthase immunoreactivity in the guinea-pig liver: distribution and colocalization with neuropeptide Y and calcitonin gene-related peptide.

AIMS/BACKGROUND: The innervation pattern of the guinea-pig liver is similar to that of the human liver. However, many aspects of the distribution of the neuronal isoform of the enzyme nitric oxide synthase (nNOS) in the guinea-pig liver and its colocalization with neuropeptides remain to be elucidated. METHODS: The distribution of nNOS was studied in fixed guinea-pig liver by light microscopic immunohistochemistry. Confocal analysis was used to determine its colocalization with neuropeptide Y (NPY) or calcitonin gene-related peptide (CGRP). RESULTS: nNOS-immunoreactive (nNOS-IR) nerves were observed in relation to hilar and interlobar vessels and in Glisson's capsule. A few nNOS-IR ganglia were observed in the extrahepatic bile duct and close to the interlobar portal triads. In addition, nNOS-IR fibers were located in the interlobular portal triads and pervading the parenchyma. Moreover, nNOS-IR nerves were demonstrated for the first time in the larger central veins and in the hepatic vein. nNOS-NPY and nNOS-CGRP colocalizations were detected in the fibromuscular layer of the bile duct and periductal plexus, respectively. CONCLUSIONS: These results support the phylogenetic conservation of the nNOS-IR hepatic innervation and its possible contribution to the regulation of hepatic blood flow and certain hepatic functions.

Immunolocalization of the HNK-1 epitope in the autonomic innervation to the liver and upper digestive tract of the developing rat embryo.

The immunohistochemical analysis of the HNK-1 epitope presence in the liver and upper digestive tract nerves was carried out in 12- to 18-day-old rat embryos embedded in acrylamide-agarose and observed with laser scanning confocal microscopy. The vagus and sympathetic trunk were intensely immunostained at all ages; branches of both structures were also HNK-1 positive, and ramified ventrocaudally following the course of the thoracic and abdominal aorta, caval vein, portal vein and ductus venosus. As early as day 12, some immunostained cells were seen in the mesentery that formed the enteric nervous system. Clearly immunostained HNK-1-immunoreactive fibres were detected innervating the digestive wall after day 14, forming both myenteric and submucosal plexuses. After day 16, the Glisson sheath showed streams of HNK-1-positive fibres coming from dorsal areas, lining the peritoneal surface of the diaphragm, invading the capsule, and ramifying superficially around the lobes of the liver. We saw no immunoreactive structures pervading the hepatic lobes at all ages studied, with the exception of occasional HNK-l-positive cells in the superficial parenchyma, which were visualized after 16 days of gestation. Our findings can help to understand the development of the gastrointestinal and liver innervation in the rat.

Molecular and kinetic characterization and cell type location of inducible nitric oxide synthase in fish.

We have found conclusive evidence for inducible nitric oxide synthase (iNOS) activity in rainbow trout (Oncorhynchus mykiss) tissue by means of biochemical, immunohistochemical, and immunoblotting analyses. This Ca(2+)-independent enzyme uses L-arginine to produce nitric oxide and L-citrulline. It was significantly inhibited by the L-arginine analogs N(omega)-monomethyl-L-arginine and N(G)-nitro-L-arginine methyl ester. Kinetic analyses showed typical Michaelian behavior with no evidence of cooperative effects. The specific activities of the liver and head kidney enzymes were 27 and 106 pmoles. min(-1). mg protein(-1), respectively, with similar values for K(m) (11 microM), all of which correspond well with the values for other previously characterized iNOS. Western blot analyses revealed a single band of M(R) = 130 kDa tested with an iNOS antiserum. At the ultrastructural level, cells with NADPH-diaphorase activity and iNOS immunoreactivity were identified as being heterophilic granulocytes in head kidney tissue and neutrophils and macrophages in hepatic tissue. The presence of an iNOS isoform in these fish tissues implies that these cells are capable of generating nitric oxide, thus pointing to the potential role of this enzyme in fish defense mechanisms.

[Aging and neurodegeneration: molecular and cellular bases]. / Envejecimiento y neurodegeneración: bases moleculares y celulares.

OBJECTIVE: A review about the possible cellular and molecular mechanisms of aging and related neurodegenerative diseases. DEVELOPMENT: The mechanisms involved in neuronal decrease, connectivity losses and glial reactivity, detected both in neurodegenerative (Alzheimer's disease) and physiological aging, are analyzed from the morphological and histological point of view to provide the morphofunctional base of the cognitive and intellectual alterations characterizing the senescence process. Taken together, these data are correlated to the possible genetical aspects implied in this process, reviewing the most relevant results on senescence and cellular death obtained from yeast, fruit fly and nematodes; besides this, a brief review of the molecular biology of gerontogenes was carried out, and the possible mechanisms inducing aging and neurodegenerative processes are analyzed according to the state-of-the-art related theories. Finally, cellular, biochemical and genetical data are correlated in the signal transduction way implied in the increase of the intracellular calcium level as the starting point of cell death. CONCLUSIONS: The main process implied in the neuronal cell death responsible for aging and the related neurodegenerative diseases are started by different agents such as the lacking of neurotrophic factors, hypoxia, hypoglycemia, excitotoxicity, and oxygen and nitrogen free radicals.

Effect of thioacetamide and dexamethasone on serum lipids in rats fed on high-fat sunflower or olive oil diets.

We have previously reported that high-fat diets develop hepatic steatosis and, depending on the fat quality, affect serum lipid levels differently (J Nutr Sci Vitaminol, 1997, 43, 155-160). The aim of this work is to study the influence of high-fat diets (14% sunflower or olive oils) on serum lipids in a model of hepatic acute damage induced by thioacetamide, and their influence when dexamethasone is administered before thioacetamide injection. Serum lipids and hepatic collagen have been evaluated using biochemical methods, and the steatotic process by histological staining. The results showed that hepatic steatosis and fibrosis are developed either by high-fat diets or thioacetamide injection. Pretreatment with dexamethasone did not decrease the hepatic collagen content. Thioacetamide injection alone or pretreatment with dexamethasone produced increase in serum tryglicerides (TG), total cholesterol (TC) and LDL-C in both high-fat diet groups, and a HDL-C increase in the olive-oil group, even though the atherogenic indices (HDL/TC and HDL/TG) were different depending on the enriched diet. The administration of high-fat diets to study the influence of the fat quality on health and disease should be interpreted carefully due to the ability of the diets themselves to cause hepatic damage.