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C Arias

Publications and source records attributed to C Arias.

At least 37 records · Page 2Linked to original sources
PubMed1998

The protein phosphatase inhibitor okadaic acid induces heat shock protein expression and neurodegeneration in rat hippocampus in vivo.

The tumor promoter okadaic acid is a potent and specific inhibitor of protein phosphatases 1 and 2A and therefore it is a useful tool for studying the participation of protein phosphorylation in cellular processes. Since it has been shown that in cultured neurons OKA behaves as a potent neurotoxin, in the present work we have administered different doses of this compound into the dorsal rat hippocampus, in order to assess its neurotoxicity in vivo. Cresyl violet staining of hippocampal sections revealed that as early as 3 h after injection of 300 ng OKA a notable neurodegeneration occurred in the CA1 subfield, the dentate gyrus, and the hilus, particularly in the former. Neuronal death was more evident at 24 h and at this time the extent of damage was dose-dependent. The process of neuronal death was accompanied by a loss of the microtubule-associated protein MAP2, as assessed by immunocytochemistry. Moreover, OKA treatment resulted in a notable expression of the inducible heat shock protein 72 in the surviving neurons of the injected hippocampus and in the corresponding CA1 and hilus of the apparently normal contralateral hippocampus. The expression of the heat shock protein was partially prevented in the injected hippocampus and completely blocked in the contralateral CA1 region, by the systemic previous administration of the NMDA receptor antagonist MK-801. These results suggest that protein hyperphosphorylation due to inhibition of phosphatases in vivo induces neuronal stress and subsequent neurodegeneration.

Animals↗
PubMed1998

Protein synthesis blockade differentially affects the stress-induced transcriptional activation of neuropeptide genes in parvocellular neurosecretory neurons.

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are synergistically interacting ACTH secretagogues that are co-expressed by parvocellular neurosecretory neurons of the hypothalamic paraventricular nucleus (PVH). To shed light on the mechanisms that mediate the stress-induced transcriptional activation of these neuropeptide genes, quantitative hybridization histochemical methods were used to assess the effects of systemic treatment with the protein synthesis inhibitor, cycloheximide, on the ether stress-induced upregulation of primary CRF and AVP transcripts, in vivo. Pretreatment with cycloheximide prevented the induction of FOS, but not CREB phosphorylation, normally seen in response to acute ether exposure, and significantly attenuated the stress-induced rise in AVP, but not CRF, heteronuclear RNA expression in the parvocellular division of the PVH. These results support the view that distinct molecular mechanisms govern the expression of the two principal corticotropin-releasing factors, in vivo.

Animals↗
PubMed1998

Influence of the purification of sodium dodecyl sulfate on the physical properties of solutions and O/W emulsions.

The effect of the purification of sodium dodecyl sulfate (SDS) has been studied in aqueous solutions and in o/w emulsions. The physical properties (surface tension, conductivity, light dispersion, viscosity, and granulometry) depend on the degree of purity of surfactant. This effect is less important within the emulsion technology when thickener or cosurfactant agents are added to the emulsion.

Chemistry, Pharmaceutical↗
PubMed1998

Lymph nodes and human tumors (review).

This review examines the crucial role of regional lymph nodes (RLN) in defense against tumor progression. RLN are one of the first major components of the immune system to come into contact with tumor cells or tumor-cell products and are important in the generation of tumor-directed immune responses. Involvement of RLN by tumor cells is a prognostic index of survival and a biological indicator of a more distant metastatic disease. Enlargement of lymph nodes as a consequence of the increase in the number of lymphoid cells, is a common finding in humans. These changes of cellular organization display the most decisive evidence of the existence of an immune response within a draining lymph node. The variety of cells mediating immune response to tumors are summarized briefly. The lymphocyte subpopulations involved reflect the nature of the response and may determine the outcome of the tumor-host interaction. The composition of the lymphocyte subpopulations can be recognized in tumor-draining lymph nodes by distinctive surface-membrane markers assessable by flow cytometry. In human patients with solid tumors limited quantification of the lymphocyte subpopulations within RLN has been carried out using this technique and the results indicated that an increase in B lymphocytes in tumor-reactive lymph nodes is marked in the adenocarcinomas (colon and breast) while in other tumors, such as melanoma and squamous cell carcinoma, this increase in B lymphocytes is less pronounced. The increased number of B lymphocytes in the reactive lymph nodes suggests the existence of an immune response involving interactions between T and B cells. B lymphocytes expression of CD80 appears to increase in some reactive lymph nodes to adenocarcinomas, possibly indicating the state of activation of CD80+ B cells, and their role as antigen-presenting cells. Any improvement in the antitumor activity of RLN would be important in the immunotherapy of cancer patients. The ability to generate a large number of tumor-reactive T lymphocytes is a critical requirement for adoptive immunotherapy. Tumor-draining lymph nodes (TDLN) are an excellent source of tumor-reactive T lymphocytes and the adoptive transfer of these cells is capable of mediating the regression of tumors established both in the lung and in the brain. Although cancers elicit a vigorous immune response during the early part of their growth, the immune response is soon downregulated, permitting progressive cancer growth. Furthermore, there are date suggesting the existence of immunosuppressive mechanisms within RLN in the antitumor response. However, there are no yet conclusive data concerning the characteristics of the response or its effectiveness.

Animals↗
PubMed1998

Glutamic acid and Alzheimer's disease.

Neurotoxicity mediated by glutamate is thought to play a role in neurological disorders such a stroke, ischemia and slowly progressing neurodegenerative diseases. However, the contribution of excitotoxicity in neuronal death that occurs in Alzheimer's disease is still an open question. This paper briefly reviews the main lines of evidence supporting a participation of excess glutamatergic neurotransmission in the neurodegeneration of selective groups of neurons in this disease.

Alzheimer Disease↗
PubMed1997

Evidence for an intramedullary prostaglandin-dependent mechanism in the activation of stress-related neuroendocrine circuitry by intravenous interleukin-1.

We have provided evidence that the stimulatory effects of intravenous interleukin-1 (IL-1) on neurosecretory neurons in the paraventricular nucleus (PVH) that express corticotropin-releasing factor (CRF) depend specifically on the integrity of catecholaminergic projections originating in caudal medulla. Here we report on experiments designed to test alternative means by which circulating IL-1 might access medullary aminergic neurons, including mechanisms involving sensory components of the vagus, the area postrema, or perivascular cells bearing IL-1 receptors. Neither abdominal vagotomy nor area postrema lesions reliably altered Fos expression induced in the medulla or PVH in response to a moderately suprathreshold dose of IL-1beta. Cytokine-stimulated increases in CRF mRNA in the PVH were also unaffected by either ablation. By contrast, systemic administration of the cyclooxygenase inhibitor indomethacin resulted in parallel dose-related attenuations of IL-1 effects in hypothalamus and medulla. Microinjections of prostaglandin E2 (PGE2; >/=10 ng) in rostral ventrolateral medulla, the principal seat of IL-1-sensitive neurons that project to the PVH, provoked discrete patterns of cellular activation in hypothalamus and medulla that mimicked those seen in response to intravenous IL-1. We interpret these findings as supporting the hypothesis that paracrine effects of PGE2 released from perivascular cells in the medulla as a consequence of IL-1 stimulation and, acting through prostanoid receptors on or near local aminergic neurons that project to the PVH, contribute to the stimulatory effects of increased circulating IL-1 on neurons constituting the central limb of the hypothalamo-pituitary-adrenal axis.

Animals↗
PubMed1997

The Pit-1 gene is regulated by distinct early and late pituitary-specific enhancers.

The differentiation of three anterior pituitary cell types is regulated by the tissue-specific POU domain factor Pit-1, which is initially expressed on Embryonic Day 13.5-14 in mice. The Pit-1 gene remains continuously, highly expressed in the somatotrope, thyrotrope, and lactotrope cells of the adult. Using the Pit-1-defective Snell dwarf as a genetic background, we demonstrate that the Pit-1 gene utilizes distinct enhancers for initial gene activation and for subsequent autoregulation (required for maintenance of expression) and that Pit-1-dependent activation of the distal enhancer can be mediated in the absence of the early enhancer. These two distinct enhancers provide the basis for temporally specific regulation by discrete pituitary-specific factors, events likely to be prototypic for regulation of other classes of genes encoding transcription factors controlling terminal differentiation.

Animals↗
PubMed1997

Neuronal damage and MAP2 changes induced by the glutamate transport inhibitor dihydrokainate and by kainate in rat hippocampus in vivo.

Neurotoxicity mediated by glutamate is thought to play a role in neurodegenerative disorders, and alterations in cytoskeletal proteins are possibly involved in the mechanisms of neuronal death occurring in Alzheimer's disease. In the present work we studied the neurotoxic effects of the intrahippocampal injections of the glutamate transport inhibitor dihydrokainate as compared to those of kainate, as well as the concomitant changes in the microtubule-associated protein MAP2. Neuronal alterations were assessed at 3, 12, 24, and 48 h by Nissl staining and immunocytochemistry of MAP2. At 3 h, both compounds induced neuronal damage that was correlated with loss of dendritic MAP2 immunoreactivity. Neuronal damage was more evident at 12 h and 24 h after drug injection, and at these times an accumulation of MAP2 in the somata of pyramidal neurons was observed. The effects of dihydrokainate were restricted to the CA1 region and totally prevented by the N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), but not by the non-NMDA receptor antagonist 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f)-quinoxaline (NBQX). In contrast, kainate-induced alterations included CA1, CA3, and CA4 subfields, and the changes in CA1 were prevented by NBQX, while MK-801 was ineffective. These results suggest that early MAP2 disruption may be a marker of the excitotoxicity due to activation of different glutamate receptors located in discrete hippocampal regions.

Animals↗
PubMed1997

Transient emotional changes elicited by intraperitoneal saline injection: effect of naloxone and flumazenil.

The effect of the intraperitoneal (i.p.) saline injection was assessed by using the defensive burying (DB) and the elevated plus-maze (EPM) anxiety paradigms in rats. Animals were handled gently by the body, injected i.p. with saline solution, 2 ml/kg, and tested independently in the defensive burying as well as in the elevated plus-maze test at different times after the i.p. injection: 1.5, 3, 5, 10, 15, and 30 min. A transient effect of i.p. saline injection was observed (i.e., increased DB in animals tested 1.5 min after injection) and a decrease in this parameter when studied 3 min after the injection. No changes at 5, 10, 15, and 30 min after the injection were found. To discriminate the putative participation of the opiate peptide and benzodiazepine receptors in the actions of the i.p. injection, flumazenil (5 mg/kg) and nalozone (1 mg/kg) were administered. The increase in DB at 1.5 min was masked by double injection, an effect blocked by naloxone, but not by flumazenil, while both of them reverted the decrease in DB response in animals tested 3 min after injection. A partial action of the i.p. in the animals tested in the elevated plus-maze test was found. Present results are discussed on the basis of behavioral and pharmacological evidence.

Animals↗
PubMed1996

[Transient osteoporosis of the hip and magnetic nuclear resonance].

The authors evaluated the diagnostic importance of MRI in a woman who presented with transient osteoporosis of both hips, over an interval of three years. The diagnosis was made only during the second episode with the aid of MRI. The patient recovered without sequelae.

Adult↗
PubMed1995

beta-Amyloid peptide fragment 25-35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices.

beta-Amyloid protein (beta AP) has been frequently associated with the neuropathology of Alzheimer's disease (AD), although the mechanisms by which it can induce neurodegeneration are still unknown. Some studies in hippocampal cultured neurons suggest that beta AP, particularly its fragment 25-35, may induce neural growth or render neurons more vulnerable to excitotoxic insults by a mechanism involving intracellular Ca2+ dyshomeostasis. We have studied the effect of fragment 25-35 on the release of endogenous amino acids from hippocampal slices of young adult (3-3.5-month-old) and aged (23-25-month-old) rats, under basal, K(+)-depolarization, and post-depolarization conditions, in the presence and absence of Ca2+. In both young and aged tissue, the basal release of amino acids was not affected by the peptide. By contrast, 1-hr preincubation of slices from young animals with 10 microM 25-35 fragment resulted in a 140% increase of glutamate and aspartate release stimulated by K+ depolarization, compared with the control-stimulated release. These effects were strictly dependent on external Ca2+. Neither the K(+)-stimulated release of gamma-amino butyric acid (GABA) nor the release of glycine, glutamine, taurine, or alanine, which was not stimulated by high K+, were affected. Substance P and a scrambled sequence of the 25-35 fragment were without any effect per se, but substance P blocked the stimulatory effect of fragment 25-35 on glutamate and aspartate release. In slices from aged rats the basal release of glutamate was significantly higher (260%) than that in young tissue, and the K(+)-induced release of both aspartate and glutamate was also higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1995

p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium. Absence of a correlation with prognostic factors.

p53 expression has been examined in 89 squamous cell carcinomas of the larynx (34 glottic, 28 supraglottic, 18 transglottic, 8 pyriform sinus, and 1 subglottic) obtained from 88 patients surgically treated in our centre. In addition, 59 laryngeal samples including normal respiratory epithelium and non-invasive squamous cell lesions were also tested. Frozen sections were immunostained with PAb 1801 and the results were correlated with pathological features, DNA ploidy and S-phase of the tumours, disease-free interval, and survival of the patients. p53 immunoreactivity was observed in 57 (64 per cent) carcinomas. None of the eight samples of normal respiratory epithelium was positive. p53-positive cells were seen in 8 of 23 (35 per cent) squamous cell metaplasias, 6 of 19 (32 per cent) low-grade dysplasias and 5 of 10 (50 per cent) high-grade dysplasias. No correlation was found between p53 expression in carcinomas and their clinical and pathological characteristics, DNA ploidy, or proliferative activity. Neither disease-free nor overall survival showed differences between p53-positive and p53-negative cases. These findings indicate that p53 may play a role in an early stage of malignant transformation of a subset of squamous cell carcinomas of the larynx, but seems not to be associated with further progression of the tumours.

Adult↗
PubMed1995

Evidence for short-loop feedback effects of ACTH on CRF and vasopressin expression in parvocellular neurosecretory neurons.

Immuno- and hybridization histochemical methods were used to examine a possible role for adrenocorticotropic hormone (ACTH) in regulating the expression of corticotropin-releasing peptides in rat hypothalamus. Densitometric assessments of relative levels of mRNAs encoding corticotropin releasing factor (CRF), arginine vasopressin (AVP) and oxytocin (OT) in the parvocellular division of the paraventricular nucleus (PVH) were carried out in intact, adrenalectomized (ADX) and hypophysectomized (HYPOX) animals. Both surgeries resulted in comparable increases in relative levels of CRF and AVP transcripts in the parvocellular PVH; no effects on OT mRNA in this compartment were evident. In a second experiment, ACTH or saline vehicle were administered systemically via osmotic minipump for seven days to rats submitted to both HYPOX and ADX surgeries. Lower replacement doses of ACTH reduced the number of detectable AVP-immunoreactive (AVP-ir) cells in the parvocellular PVH to 53% of that seen in vehicle-treated HYPOX/ADX controls; the number of CRF-IR cells was not significantly affected. Higher doses of ACTH resulted in counts of AVP- and CRF-IR neurons that were reduced to 32% and 70%, respectively, of control values. Staining patterns for the two peptides in the external lamina of the median eminence generally followed the cell count data. Neither densitometric nor combined immunohistochemical (for CRF-ir) and hybridization histochemical (for AVP mRNA) assays revealed any marked effect of ACTH on AVP mRNA expression in the parvocellular PVH of HYPOX/ADX rats. The results indicate that ACTH is capable of inhibiting corticotropin-releasing peptide, but not mRNA, expression in hypophysiotropic neurons. The mechanisms underlying these effects remain to be fully clarified.

Adrenocorticotropic Hormone↗
PubMed1993

Okadaic acid induces early changes in microtubule-associated protein 2 and tau phosphorylation prior to neurodegeneration in cultured cortical neurons.

Microtubules and their associated proteins play a prominent role in many physiological and morphological aspects of brain function. Abnormal deposition of the microtubule-associated proteins (MAPs), MAP2 and tau, is a prominent aspect of Alzheimer's disease. MAP2 and tau are heat-stable phosphoproteins subject to high rates of phosphorylation/dephosphorylation. The phosphorylation state of these proteins modulates their affinity for tubulin and thereby affects the structure of the neuronal cytoskeleton. The dinoflagellate toxin okadaic acid is a potent and specific inhibitor of protein phosphatases 1 and 2A. In cultured rat cortical neurons and a human neuroblastoma cell line (MSN), okadaic acid induces increased phosphorylation of MAP2 and tau concomitant with early changes in the neuronal cytoskeleton and ultimately leads to cell death. These results suggest that the diminished rate of MAP2 and tau dephosphorylation affects the stability of the neuronal cytoskeleton. The effect of okadaic acid was not restricted to neurons. Astrocytes stained with antibodies to glial fibrillary acidic protein (GFAP) showed increased GFAP staining and changes in astrocyte morphology from a flat shape to a stellate appearance with long processes.

Animals↗
PubMed1992

The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization.

In addition to a nonadecapeptide homologous to the teleost melanin-concentrating hormone (MCH), the amino acid sequence predicted from a rat prepro-MCH (ppMCH) cDNA suggested that at least one (neuropeptide EI, or NEI), and possibly a second (NGE), additional neuropeptide may be encoded by this precursor. Cross-reactivity with epitopes of NEI or NGE can account for reported localization of alpha-MSH, rat CRF, and human GRF in rat dorsolateral hypothalamic neurons. We have used antisera raised against rat MCH and NEI in immunohistochemical studies at the light and electron microscopic levels, along with hybridization histochemical localization of ppMCH mRNA, to define the organization of this system. As expected, ppMCH mRNA is prominently expressed in cells in the lateral hypothalamic area and zona incerta. The MCH and NEI peptides were extensively colocalized in neurons in both of these areas. In addition, smaller cell groups in the olfactory tubercle and pontine tegmentum were also positively hybridized for ppMCH mRNA and immunostained for MCH and NEI. Fibers stained for MCH and NEI were similarly, and very broadly, distributed throughout the central nervous system in patterns that generally conformed with known projection fields of the lateral hypothalamic area and zona incerta. A differential distribution was seen in at least one region, the interanterodorsal nucleus of the thalamus, which contained a prominent terminal field stained for MCH but not NEI. At the electron microscopic level, MCH-stained perikarya displayed a prominent staining associated with the Golgi apparatus; this was not encountered in NEI-stained cells. Both peptides were distributed similarly in terminals in the lateral hypothalamic area and median eminence, with staining associated principally with dense-cored vesicles. The results suggest that ppMCH-derived peptides may serve as neurotransmitters or modulators of prominence in a surprisingly expansive projection field of incerto-hypothalamic neurons. The terminal distributions of this system seem most compatible with functional roles in generalized arousal and sensorimotor integration, processes previously implicated as being subject to modulation by the lateral hypothalamic area.

Animals↗
PubMed1992

Inhibition of brain glutamate decarboxylase activity is related to febrile seizures in rat pups.

Because previous work showed that in the newborn brain, but not in the adult brain, glutamate decarboxylase (GAD) is notably susceptible to heat, we have studied the possible involvement of GAD inhibition in febrile convulsions and the related changes in gamma-aminobutyric acid (GABA) content. Rats of different ages were subjected to hyperthermia, and GAD activity was determined in brain homogenates by measuring the release of 14CO2 from labeled glutamate and by measuring the formation of GABA. The latter method gave considerably lower values than the former in the youngest rats, and was considered more reliable. With this method, we found a 37-48% inhibition of GAD activity in rat pups 2-5 days old, which showed febrile seizures at progressively higher body temperatures, whereas in 10- and 15-day-old animals, which did not show convulsions, GAD activity was not affected by hyperthermia. Whole-brain GABA levels, however, did not change at any age. In contrast to GAD, choline acetyltransferase and lactic dehydrogenase activities were not altered by hyperthermia at any of the ages studied. These results suggest that a decreased efficiency of the inhibitory neurotransmission mediated by GABA, consequent to the inhibition of GAD activity, may be a factor related to febrile convulsions.

Animals↗