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Biomedical subjects

I Ferrer

Publications and source records attributed to I Ferrer.

At least 163 records · Page 9Linked to original sources
PubMed1998

BDNF up-regulates TrkB protein and prevents the death of CA1 neurons following transient forebrain ischemia.

The neurotrophin family of growth factors, which includes Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT3) and Neurotrophin-4/5 (NT4/5) bind and activate specific tyrosine kinase (Trk) receptors to promote cell survival and growth of different cell populations. For these reasons, growing attention has been paid to the use of neurotrophins as therapeutic agents in neurodegeneration, and to the regulation of the expression of their specific receptors by the ligands. BDNF expression, as revealed by immunohistochemistry, is found in the pre-subiculum, CA1, CA3, and dentate gyrus of the hippocampus. Strong TrkB immunoreactivity is present in most CA3 neurons but only in scattered neurons of the CA1 area. Weak TrkB immunoreactivity is found in the granule cell layer of the dentate gyrus. Unilateral grafting of BDNF-transfected fibroblasts into the hippocampus resulted in a marked increase in the intensity of the immunoreaction and in the number of TrkB-immunoreactive neurons in the granule cell layer of the dentate gyrus, pre-subiculum and CA1 area in the vicinity of the graft. No similar effects were produced after the injection of control mock-transfected fibroblasts. Delayed cell death in the CA1 area was produced following 5 min of forebrain ischemia in the gerbil. The majority of living cells in the CA1 area at the fourth day were BDNF/TrkB immunoreactive. Unilateral grafting of control mock-transfected or BDNF fibroblasts two days before ischemia resulted in a moderate non-specific protection of TrkB-negative, but not TrkB-positive cells, in the CA1 area of the grafted side. This finding is in line with a vascular and glial reaction, as revealed, by immunohistochemistry using astroglial and microglial cell markers. This astroglial response was higher in the grafted side than in the contralateral side in ischemic gerbils, but no differences were seen between BDNF-producing and non-BDNF-producing grafts. However, grafting of BDNF-producing fibroblasts two days before ischemia significantly and specifically prevented nerve cells from dying in the CA1 area of the ipsilateral hippocampus. Cell survival was associated with increased TrkB immunoreactivity as the majority of living cells were TrkB immunoreactive. Thus, our results show that BDNF is able to up-regulate the expression of TrkB in control and pathological states, and that BDNF prevention of neuronal death following transient forebrain ischemia is associated with increased expression of its specific receptor.

Animals↗
PubMed1998

Molecular diagnosis of lecithin: cholesterol acyltransferase deficiency in a presymptomatic proband.

We report the molecular diagnosis of a lecithin : cholesterol acyltransferase deficiency in a 12-year old proband with a high-density lipoprotein deficiency. The increased percentage of free cholesterol in plasma and high-density lipoprotein indicated an inherited lecithin : cholesterol acyltransferase deficiency as the underlying cause. This diagnosis was confirmed by a low plasma lecithin : cholesterol acyltransferase activity and a combination of genetic analyses which demonstrated compound heterozygosity for two mutations in the lecithin : cholesterol acyltransferase gene of the proband. One was a previously unreported 2 bp deletion leading to a stop signal in codon 77 and the other a point mutation causing Arg 135-->Gln transition. To our knowledge, this is the first diagnosis of lecithin : cholesterol acyltransferase deficiency in a pre-symptomatic patient. Whether the proband will develop signs of complete lecithin : cholesterol acyltransferase deficiency or the milder form (Fish Eye Disease) is uncertain, although the former possibility is more likely. The risk of premature atherosclerosis conferred by lecithin : cholesterol acyltransferase deficiency is not well established. The proband will need to be carefully monitored in the future.

Child↗
PubMed1998

Effect of summer intermission on skeletal muscle of adolescent soccer players.

BACKGROUND: To study the effect of some weeks of rest on three groups of adolescent soccer players, who had undergone systematic training for eleven months. METHODS EXPERIMENTAL DESIGN: Retrospective and comparative investigation; duration 4-8 weeks. SETTING: young amateur players from a Spanish football club were examined at the beginning and at the end of the summer rest period. PARTICIPANTS: 37 young soccer players aged 14, 15 and 16 years old. They were members of three football teams. INTERVENTIONS: during the rest period they were free from any training program. MEASURES: biopsies of M. vastus lateralis were taken immediately after training and after the summer holidays. The type, percentage and diameter of the fibers, as well as the enzymes of glycogen metabolism (glycogen synthase and glycogen phosphorylase), glycolysis (phosphofructokinase and lactate dehydrogenase), oxidative metabolism (succinate dehydrogenase and citrate synthase) and creatine kinase and transaminase (aspartate and alanine aminotransferase) were studied. RESULTS: Detraining had an adaptation effect, decreasing the cross-sectional area of type I and type II fibers, and decreasing the activities of creatine kinase, citrate synthase, phosphofructokinase, lactate dehydrogenase and aspartate aminotransferase. CONCLUSIONS: The results can help trainers to plan the length of the rest period between training.

Adaptation, Physiological↗
PubMed1997

Bcl-2 and Bax proteins in Lewy bodies from patients with Parkinson's disease and Diffuse Lewy body disease.

Double-labelling immunohistochemistry of Bcl-2 and Bax, and ubiquitin (as a marker of Lewy bodies) was examined in the brains of patients with Parkinson's disease and Diffuse Lewy body disease to learn about possible modifications of protein expression and the presence of Lewy bodies. Bcl-2 and Bax immunoreactivities were observed in Lewy body-bearing and non-Lewy body-bearing neurons in patients with parkinsonism. These results show that Bcl-2 and Bax are probably not implicated in Lewy body formation and that the presence of Lewy bodies does not have a direct impact on the expression of Bcl-2 and Bax proteins in individual neurons.

Aged↗
PubMed1997

Identification of ionic chloroacetanilide-herbicide metabolites in surface water and groundwater by HPLC/MS using negative ion spray.

Solid-phase extraction (SPE) was combined with high-performance liquid chromatography/high-flow pneumatically assisted electrospray mass spectrometry (HPLC/ ESP/MS) for the trace analysis of oxanilic and sulfonic acids of acetochlor, alachlor, and metolachlor. The isolation procedure separated the chloroacetanilide metabolites from the parent herbicides during the elution from C18 cartridges using ethyl acetate for parent compounds, followed by methanol for the anionic metabolites. The metabolites were separated chromatographically using reversed-phase HPLC and analyzed by negative-ion MS using electrospray ionization in selected ion mode. Quantitation limits were 0.01 microgram/L for both the oxanilic and sulfonic acids based on a 100-mL water sample. This combination of methods represents an important advance in environmental analysis of chloroacetanilide-herbicide metabolites in surface water and groundwater for two reasons. First, anionic chloroacetanilide metabolites are a major class of degradation products that are readily leached to groundwater in agricultural areas. Second, anionic metabolites, which are not able to be analyzed by conventional methods such as liquid extraction and gas chromatography/mass spectrometry, are effectively analyzed by SPE and high-flow pneumatically assisted electrospray mass spectrometry. This paper reports the first HPLC/MS identification of these metabolites in surface water and groundwater.

Acetamides↗
PubMed1997

Stability of pesticides stored on polymeric solid-phase extraction cartridges.

The stability of four pesticides (desethylatrazine, fenamiphos, fenitrothion and fonofos) was examined under different storage conditions after preconcentration in disposable solid-phase extraction (SPE) cartridges containing new polymer sorbent materials (Hysphere-1, IST EnviroLut and LiChrolut). Complete recovery for all the compounds was observed in precolumns kept at -20 degrees C for 1 month when preconcentrating 26 ml of ground water sample spiked at 10 micrograms/l. Degradation of fenamiphos and fenitrothion occurred in precolumns stored at 4 degrees C and at room temperature after 1 month. Fonofos was stable when compared to their storage in C18 precolumns. Problems in the quantification of the analytes after storage at 4 degrees C and at room temperature were encountered due to the presence of many interfering peaks in the chromatograms. Analysis of blanks with C18 precolumns was carried out, to determine the interferences. The stability of the pesticides was also examined in acidifed and non-acidified ground water in order to compare it to the stability of pesticides stored on SPE cartridges. Significant losses of fenamiphos and fenitrothion were achieved and were related to the pH of the water sample and their chemical structure. Finally, the new polymeric sorbent Hysphere-I was evaluated in terms of breakthroughs and compared with those of C18, obtaining higher recoveries for desethylatrazine.

Atrazine↗
PubMed1997

Transient forebrain ischemia in the adult gerbil is associated with a complex c-Jun response.

C-Jun expression in the hippocampus of gerbils subjected to 5 min of transient forebrain ischemia was examined with immunohistochemistry and western blotting using two c-Jun antibodies raised against two different amino acid sequences. Both c-Jun antibodies showed increased immunoreactivity at 6 and 12 h postischemia in the stratum pyramidale of CA3 and granule cell layer of the dentate gyrus. No immunostaining was detected in CA1 up to the 7th day. Western blots showed increased c-Jun immunoreactivity at 6 and 12 h. However, the antibody c-Jun (AB-1) detected a single band at about p39 in normal and post-ischemic states, whereas the antibody c-Jun/AP-1 (N) recognized a band at about p39 in normal and post-ischemic gerbils, and a p62 phosphorylated double-band at 6 and 12 h following ischemia. In addition, increased c-Jun N-terminal kinase-1 (JNK-1) expression was observed on western blots at 6 and 12 h postischemia. These results suggest that different c-Jun-related responses, some of which probably indicate post-translational changes of the c-Jun protein, occur in the hippocampus of the gerbil following transient forebrain ischemia.

Animals↗
PubMed1997

Identification of necrotic cell death by the TUNEL assay in the hypoxic-ischemic neonatal rat brain.

The time course and localization of DNA fragmentation in a neonatal rat model of unilateral hypoxia-ischemia were assessed by means of the terminal transferase-mediated biotin dUTP nick end labeling (TUNEL) assay. TUNEL-positive cells were detected in the hemisphere ipsilateral to the ligation immediately after the injury and increased to reach a maximum 1-3 days later, then decreasing until day 10, in parallel with cell death identified by standard histological methods. Cells showing any of the different morphologies of chromatin condensation and fragmentation were labeled, particularly within the core of the ischemic lesion. These results, obtained in a paradigm of necrosis in the immature brain, add to previous evidence suggesting that some forms of non-apoptotic DNA fragmentation are labeled by the TUNEL assay.

Animals↗
PubMed1997

L-Deprenyl does not reduce brain damage in global forebrain ischemia in adult gerbils (Meriones ungiculatus).

Delayed neuronal death is produced at about the 4th day following global forebrain ischemia. This study investigates whether L-deprenyl, an irreversible and selective MAO-B inhibitor, reduces brain damage following global forebrain ischemia in adult gerbils. For this purpose, global forebrain ischemia was induced in adult gerbils by occlusion for 5 min of both common carotid arteries. L-Deprenyl, 10 mg/kg weight in saline (10 mg/ml) i.p., was administered 1 h after or 2 h before occlusion, followed by daily administration for 4 days. Treated animals were processed in parallel with ischemic animals receiving saline alone, and with sham-operated controls. Counts of viable neurons were made in the pyramidal cell layer of the CA1 region of the hippocampus at the 4th day after the ischemic episode. The number of viable neurons in the pyramidal cell layer of CA1 was similar in animals treated with L-deprenyl or saline alone (Mann-Whitney U-test, alpha=0.05 two-tailed). The present results show that L-deprenyl does not prevent neuronal cell death following global forebrain ischemia in the adult gerbil when the administration of the drug is started shortly after or shortly before the ischemic episode.

Age Factors↗
PubMed1997

Stat1 in developing and adult rat brain. Induction after transient focal ischemia.

Stat1 has a dual function as signal transducer and activator of transcription, and is activated in response to growth factors and cytokines. We examined Stat1 in the rat brain during development and following transient focal ischemia, using Western immunoblotting. Two bands of 91 and 84 kDa, corresponding to Stat1 alpha and Stat1 beta forms, were found with an intensity that increased from postnatal day 0 to adulthood in cerebellum and cerebral cortex. Ischemia caused a strong induction of Stat1 in the ipsilateral cortex after 4, 7 and 15 days, but not at 6 or 24 h. These results show that Stat1 is normally expressed in the postnatal and adult rat brain and is induced under brain infarction.

Animals↗
PubMed1997

bFGF and FGFR-3 immunoreactivity in the rat brain following systemic kainic acid administration at convulsant doses: localization of bFGF and FGFR-3 in reactive astrocytes, and FGFR-3 in reactive microglia.

Strong bFGF immunoreactivity was observed in reactive astrocytes, as shown by double-labeling immunohistochemistry of bFGF and GFAP, from days 7 up to 30 (last time point examined) following kainic acid (KA) injection at convulsant doses in the adult rat. bFGF was not found in OX-42-positive reactive microglia. A few reactive glia co-localized FGFR-3 and GFAP, whereas the majority of cells expressing FGFR-3 were OX-42-immunoreactive. This was further supported by the observation that only approximately 10% of reactive glia co-localized bFGF and FGFR-3. These results show that reactive astrocytes are a major source of bFGF during the subacute stages of tissue damage following KA injection and that reactive astrocytes and, most particularly, reactive microglia are putative targets of bFGF through FGFR-3.

Animals↗
PubMed1997

Cortical infarct volume is dependent on the ischemic reduction of perifocal cerebral blood flow in a three-vessel intraluminal MCA occlusion/reperfusion model in the rat.

Occlusion of the middle cerebral artery (MCA) causes a reduction of cerebral blood flow (CBF), which shows a progressive decrease from the periphery to the core of the MCA territory. The severity of ischemia is dependent on the duration of the ischemic episode and degree of CBF reduction. Fixing the ischemic episode to 1 h, we have examined whether or not cortical infarct size was related to the degree of CBF reduction in a perifocal cortical area in rats. One-hour intraluminal MCA occlusion accompanied with bilateral common carotid artery (CCA) occlusion (three-vessel occlusion/reperfusion model) was carried out in Sprague-Dawley rats and CBF was monitored with laser-Doppler flowmetry in the fronto-parietal cortex, an area which is perifocal to the core of the MCA territory. Finally, infarct size was measured 7 days later and was related to the corresponding CBF decrease. Sequential ipsilateral CCA, MCA and contralateral CCA occlusions produced reductions of CBF to 96%, 52% and 33% of baseline, respectively. Cortical infarct volume was found to be dependent on the corresponding reduction of perifocal cortical CBF during the ischemic episode. These results show that the reduction of CBF in the periphery of the MCA territory during 1-h focal ischemia determines infarct size in a three-vessel occlusion/reperfusion model.

Animals↗
PubMed1997

Immunocytochemical analysis of the synaptic proteins SNAP-25 and Rab3A in human pituitary adenomas. Overexpression of SNAP-25 in the mammmosomatotroph lineages.

SNAP-25 and Rab3A were originally identified as synaptic proteins involved in neuronal membrane traffic. Recently, both proteins have been detected in several mammalian endocrine cell types and have been proposed as essential components of the exocytotic pathway in neuroendocrine cells. In this study, the expression of SNAP-25 and Rab3A was analysed in biopsied human anterior pituitary tumours (21 cases) by immunocytochemical methods. No differences in Rab3A immunoreactivity were observed between tumour and normal pituitary cells. Strong SNAP-25 immunoreactivity was detected in tumour cells of prolactinomas (n = 3). Several growth hormone (GH)/prolactin (PRL) tumours also displayed intense SNAP-25 immunolabelling (n = 3), whereas the remaining GH-secreting adenomas (n = 4) exhibited moderate to weak SNAP-25 immunoreactivity. In contrast, SNAP-25 near-background immunostaining was observed in tumour cells of adrenocorticotrophic hormone (ACTH)-secreting tumours (n = 4) and non-secreting tumours (n = 7), as well as in normal pituitary cells. Since SNAP-25 and Rab3A have been shown to be involved in exocytotic events in rodent endocrine cells, overexpression of SNAP-25 protein in PRL and GH/PRL tumour cells might be implicated in the mechanism of exocytosis of the neoplastic human mammosomatotroph lineages.

Acromegaly↗
PubMed1997

Apoptosis is not the mechanism of cell death of muscle fibers in human muscular dystrophies and inflammatory myopathies.

Muscle biopsies from patients affected by muscular dystrophies and polymyositis were processed with the method of in situ labeling of nuclear DNA fragmentation in order to assess whether apoptosis occurs in these diseases. Apoptotic nuclei were seen in the mononuclear cell infiltrates in inflammatory myopathies but not in dying muscle fibers, thus confirming the general opinion that death of muscle fibers in human diseases is not produced by a mechanism of apoptosis.

Animals↗
PubMed1997

Striatal infarction in the rat causes a transient reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra.

Dopaminergic neurons of the substantia nigra pars compacta were examined in the rat brain following striatal infarction subsequent to transient focal cerebral ischemia. Rats had the middle cerebral artery occluded for 2 h or were sham-operated, and tyrosine hydroxylase immunoreactivity was evaluated by Western blot and immunohistochemistry at different times ranging from 1 to 60 days after ischemia. The number of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta was counted under the light microscope and compared to that in the contralateral side and controls. No changes of tyrosine hydroxylase immunoreactivity were detected in the ipsilateral versus the contralateral substantia nigra of sham-operated rats or 1 day after ischemia. However, a statistically significant reduction of tyrosine hydroxylase-immunoreactive cells became apparent in the ipsilateral compared with the contralateral substantia nigra at 7 and 14 days after ischemia. This reduction showed a clear recovery at 30 days after ischemia, and no signs of difference between the ipsilateral and the contralateral side were apparent by 60 days. Therefore, the reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra was only transiently seen from 1 to 2 weeks following ischemia. The observed loss of tyrosine hydroxylase was not accompanied by signs of cell death or gliosis in the ipsilateral pars compacta. The present results show a transitory reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra pars compacta after focal ischemia and suggest that striatal infarction causes a transient deficit of dopaminergic function.

Animals↗
PubMed1997

Spinal muscular atrophy in Holstein-Friesian calves.

The clinical and neuropathological findings of spinal muscular atrophy (SMA) in Holstein-Friesian calves are described in four females and one male from a dairy farm composed of 150 cows and 2 breeding bulls. Locomotion difficulties started at the age of 15 days, and progressed to paraparesis and tetraparesis in 2 weeks. Signs consistent with denervation were revealed with electromyography. The neuropathological examination showed degeneration and loss of motor neurons in the spinal cord, together with astrocytosis. Among the remaining motor neurons were ghost cells and neurons filled with accumulations of straight filaments measuring 10-12 nm in diameter, which were strongly immunoreactive with antibodies produced against phosphorylated neurofilaments. Degenerating cells in SMA did not stain with the method of in situ labelling of nuclear DNA fragmentation and did not show c-Jun immunoreactivity. This feature contrasts with the in situ labelling of DNA breaks of apoptotic cells and with the strong c-Jun immunoreactivity restricted to dying cells during the whole process of naturally occurring cell death in the developing central nervous system. These features suggest that cell death in SMA differs from programmed cell death during normal development, and that pathological cell death in SMA should not be considered as a mere persistence or reactivation of normally occurring developmental cell death.

Animals↗
PubMed1997

Ubiquitination of apoptotic cells in the developing cerebellum of the rat following ionizing radiation or methylazoxymethanol injection.

Previous studies have shown ubiquitin mRNA induction and protein expression associated with regressive phenomena in some cases of developmentally programmed cell death and experimentally induced apoptosis. Ubiquitin immunoreactivity was examined in the developing cerebellum of the rat following ionizing radiation or methylazoxymethanol (MAM) injection. In irradiated rats, apoptotic cells in the external granule cell layer appeared at 3 h, peaked at 6 h, and decreased thereafter to reach nearly normal values at 48 h. In MAM-treated rats, apoptotic cells in the external granule cell layer were seen at 24 h, peaked at 48 h, and decreased at 72 h. Strong ubiquitin expression was observed in about 15% of apoptotic cells at later stages of apoptosis in both experimental models of induced cell death. In irradiated rats, strong ubiquitin immunoreactivity in apoptotic cells and cellular debris was observed 12 h after irradiation, peaking at 24 h, and decreasing at 48 h. In MAM-treated rats, strong ubiquitin immunoreactivity was found in apoptotic cells and cellular debris at 48 h and decreased at 72 h. Results suggest that activation of the ubiquitin pathway is not a signal that triggers apoptosis but rather a final step in the apoptotic process.

Alkylating Agents↗