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Biomedical subjects

R Cortés

Publications and source records attributed to R Cortés.

At least 19 recordsLinked to original sources

Reversion of levodopa-induced motor fluctuations by the A2A antagonist CSC is associated with an increase in striatal preprodynorphin mRNA expression in 6-OHDA-lesioned rats.

The molecular mechanisms involved in the reversion of levodopa-induced motor fluctuations by the adenosine A2A antagonist 8-(3-chlorostryryl) caffeine (CSC) were investigated in rats with a 6-hydroxydopamine (6-OHDA)-induced lesion and compared with the ones achieved by the kappa-opioid agonist, U50,488. Animals were treated with levodopa (50 mg/kg/day) for 22 days and for one additional week with levodopa + CSC (5 mg/kg/day), levodopa + U50,488 (1 mg/kg/day), or levodopa + vehicle. The reversion of the decrease in the duration of levodopa-induced rotations by CSC, but not by U50,488, was maintained until the end of the treatment and was associated with a further increase in levodopa-induced preprodynorphin mRNA in the lesioned striatum, being higher in the ventromedial striatum. The increase in striatal preprodynorphin expression, particularly in the ventromedial striatum, may be related to the reversion of levodopa-induced motor fluctuations in the CSC-treated animals, suggesting a role of the direct striatal output pathway activity in the ventromedial striatum in the pathophysiology of motor fluctuations.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Observation of a Mott insulating ground state for Sn/Ge(111) at low temperature.

We report an investigation on the properties of 0.33 ML of Sn on Ge(111) at temperatures down to 5 K. Low-energy electron diffraction and scanning tunneling microscopy show that the (3x3) phase formed at approximately 200 K, reverts to a new ((square root 3)x(square root 3))R30 degrees phase below 30 K. The vertical distortion characteristic of the (3x3) phase is lost across the phase transition, which is fully reversible. Angle-resolved photoemission experiments show that, concomitantly with the structural phase transition, a metal-insulator phase transition takes place. The ((square root 3)x(square root 3))R30 degrees ground state is interpreted as the formation of a Mott insulator for a narrow half-filled band in a two-dimensional triangular lattice.

Journal Article↗

Could the homologous sequence of anti-inflammatory pentapeptide (MLIF) produced by Entamoeba histolytica in the N protein of rabies virus affect the inflammatory process?

Amebiasis and rabies are public health problems, and they have in common a poor inflammatory effect in the target organs that they affect. In the GenBank, it was found that the anti-inflammatory peptide monocyte locomotion inhibitory factor (MLIF) produced by Entamoeba histolytica homologates 80%, with a fragment of the N protein of the rabies virus. We speculated if the N protein could contribute to the scant inflammatory reaction produced by rabies virus in central nervous system. The N protein was obtained and studied in vitro and in vivo. The N protein, as MLIF, inhibited the respiratory burst in human mononuclear phagocytes (43%, p<0.05), but in contrast to MLIF, it increased chemotaxis and it did not significantly inhibit delayed hypersensitivity skin reaction to 1-chloro-2-4-dinitrobenzene in guinea pigs. Therefore, the full peptide sequence has to be present or it has to be cleaved-free from the large recombinant N protein molecule (55 kDa) to become active.

Animals↗

The kappa opioid agonist U50,488 potentiates 6-hydroxydopamine-induced neurotoxicity on dopaminergic neurons.

Several observations support the hypothesis that kappa opioid (kappa-opioid) receptor agonism may contribute to neurotoxicity, but other reports have suggested that certain kappa-agonists can attenuate neurological dysfunction. Degeneration of dopaminergic neurons in the substantia nigra is the pathological hallmark of Parkinson's disease. Therefore, it is of particular interest to study whether kappa-opioid receptor agonism has an influence on the progressive degeneration of dopaminergic neurons. We have investigated the effect exerted by the selective kappa-agonist U50,488 on the neurotoxicity induced by intrastriatal 6-hydroxydopamine (6-OHDA) administration on dopaminergic neurons. Male Sprague-Dawley rats received an acute (0.5 mg/kg) or subacute (0.5 mg/kg, twice at day, for 7 days) administration of U50,488, receiving the last dose 30 min before intrastriatal 6-OHDA administration. Acute or subacute U50,488 pretreatment potentiated the 6-OHDA-induced decrease in the number of nigral tyrosine hydroxylase immunoreactive neurons (P < 0.05). Acute U50,488 pretreated animals showed a tendency, although not statistically significant to increase striatal mRNA encoding for enkephalin (PPE mRNA). Subacute U50,488 significantly potentiated the increase in PPE mRNA induced by 6-OHDA (P < 0.05). The present results show a neurotoxic effect of the kappa agonist U50,488 on dopaminergic neurons in rats with a striatal lesion induced by 6-OHDA. This neurotoxic effect is associated to an increase in striatal PPE mRNA levels, suggesting that an increase in the indirect pathway activity and consequently an increase in the activity of the subthalamo-nigral pathway might be involved in this phenomenon.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization.

Phosphodiesterases (PDEs) play a central role in signal transduction by regulating intracellular levels of cyclic AMP (cAMP) and cGMP. It has been suggested that cAMP pathways could be upregulated in Alzheimer's disease. By in situ hybridization histochemistry we have determined the expression pattern of two newly described cAMP-specific phosphodiesterases families, PDE7 and PDE8, in several brain areas in control subjects. The hybridization levels of PDE8A mRNA were very low in all brain areas examined. High PDE7B and PDE8B mRNA signal intensities were found in the hippocampal formation. PDE7A was found to be present in both neuronal and non-neuronal cell populations. When the expression of these isozymes in control brains was compared with that in Alzheimer's disease brains staged according to Braak and Braak (Acta Neuropathol. (Berl.) 82 (1991), 239), we found that PDE8B was the only isozyme showing a significant increase, in cortical areas and parts of the hippocampal formation, at Braak stages III-VI. Our results show that the expression of specific cAMP PDE isoforms is selectively regulated in Alzheimer's disease and associated with the stages of the disease. The availability of animal models of Alzheimer's disease and of new pharmacological tools such as selective PDE inhibitors will allow study of the therapeutic potential of the control of cAMP levels in AD.

3',5'-Cyclic-AMP Phosphodiesterases↗

Dicubane-like tetrameric cobalt(II)-pseudohalide ferromagnetic clusters.

Three tetrameric cobalt(II)-pseudohalide complexes have been structurally and magnetically characterized. Compounds 1 and 2 are isomorphous and exhibit the general formula [Co2(dpk-OH)(dpk-CH3O)(L)(H2O)]2A2-4H2O where dpk = di-2-pyridyl ketone, L = N3(-) and A = BF4(-) for 1, and L = NCO(-) and A = ClO4(-) for 2. The ligands dpk-OH(-) and dpk-CH3O(-) result from solvolysis and ulterior deprotonation of dpk in water and methanol, respectively. Both compounds exhibit cationic tetramers consisting of a dicubane-like core with two missing vertexes where the Co(II) ions are connected through end-on pseudohalide and oxo-bridges. A similar tetranuclear core has been found for 3 whose formula is [Co2(dpk-OH)(dpk-CH3O)(NCO)2]2. In this case, the tetramers are neutral and exhibit a terminal cyanate in place of the coordinated molecule of water for 1 and 2. The tetrameric units for 2 and 3 represent the first examples of any kind of cubanes exhibiting cyanate bridges as well as the first Co(II) compounds exhibiting intermetallic bridges through these pseudohalide groups. Measurements of the magnetic susceptibility indicated the presence of ferromagnetic Co(II)-Co(II) interactions in the three compounds.

Journal Article↗

Weak M(II)-azide-4,4'-bipy ferromagnets based on unusual diamondoid (M = Mn) and 2D arrays (M = Co, Ni).

Four compounds of general formula [M(4,4'bipy)(N(3))2](n) (M = Mn (1), Zn (2), Co (3), Ni (4)) have been synthesized and magnetostructurally characterized by means of X-ray diffraction analysis, IR and ESR spectroscopies, and measurements of the magnetic susceptibility and magnetization. Compound 1 (C(10)H(8)N(8)Mn) crystallizes in the tetragonal P4(3)2(1)2 space group, Z = 4, with a = 8.229(2), b = 8.229(2), and c = 16.915(2) A. It exhibits an acentric 3D structure where Mn(II) ions are linked through EE-azide groups resulting in a diamondoid network. The 4,4'bipy ligands are coordinated on the axial positions of the octahedral spheres reinforcing the intermetallic connections. Weak ferromagnetism arising from spin canting is observed for compound 1. Compounds 2, 3, and 4 are proposed to be isomorphous and would consist of a 2D array where alternating EO + EE/EO + EE/EO + EO azide-chains are linked by 4,4'bipy ligands resulting in pi-pi stacked pyridyl-columns. The azido ligand dispositions in compounds 3 and 4 make possible systems of type -AF-AF-F-, which would give rise to a topological ferromagnetic behavior.

Journal Article↗

Structural analysis and magnetic properties of the 1D and 3D compounds [Mn(dca)2nbipym] (M = Mn, Cu; dca = dicyanamide; bipym = bipyrimidine; n = 1,2).

Compounds [Mn(dca)2bipym] (1), [Cu2(dca)4bipym] (2), and [Mn2(dca)4bipym] (3) have been synthesized and structural (2, 3) and magnetically characterized. Compound 1 is isomorphous with [Mn(dca)2bipy]. Compound 2 crystallizes in the monoclinic P2(1)/c space group, Z = 4, with a = 7.5609(9), b = 11.477(42), and c = 11.792(2) A and beta = 106.565(6) degrees. Compound 3 crystallizes in the monoclinic system, space group P2(1)/n, with a = 7.396(3) A, b = 11.498(7) A, and c = 12.349(9) A and beta = 106.61(5) degrees. While compound 1 is one-dimensional, with the manganese(II) ions bridged by double mu1,5-dicyanamide ligands, the structural arrangement in compounds 2 and 3 is three-dimensional based on ladder-like moieties. These units, whose steps are bipym groups, extend through mu1,5-dca bridges and are connected to another four on the plane perpendicular to the extension of the ladders to form the 3D arrangement. Magnetic susceptibility measurements show antiferromagnetic couplings in all cases, increasing for 1, 3, and 2, respectively.

Journal Article↗

Polyamines in the basal ganglia of human brain. Influence of aging and degenerative movement disorders.

The distribution of polyamines in the human basal ganglia was examined, using dansyl-derivatives and high pressure liquid chromatography with fluorimetric detection. A heterogeneous distribution of putrescine, spermidine (SD) and spermine (SM) was observed in control brains. A consistent negative correlation between SD and SM content and age was found in different brain areas. These results suggest an involvement of polyamines in age-related changes occurring in white-matter. When the influence of degenerative movement disorders -Parkinson's disease, Huntington's disease (HD) and progressive supranuclear palsy- was analyzed, significant changes were observed only in HD, where a decrease in the concentration of SM was found in the putamen. These results suggest that in advanced stages of neurodegenerative processes, polyamines maintain their regulation. Only in the presence of severe atrophy, SM concentration is reduced.

Aged↗

Synthesis and antiparasitic activity of 2-(trifluoromethyl)-benzimidazole derivatives.

2-(Trifluoromethyl)benzimidazole derivatives substituted at the 1-, 5-, and 6-positions have been synthesized and in vitro tested against the protozoa Giardia lamblia, Entamnoeha histolytica. and the helminth Trichinella spiralis. Results indicate that all the compounds tested are more active as antiprotozoal agents than Albendazole and Metronidazole. One compound (20) was as active as Albendazole against T. spiralis. These compounds were also tested for their effect on tubulin polymerization and none inhibited tubulin polymerization.

Animals↗

Total arsenic, lead, cadmium, copper, and zinc in some salt rivers in the northern Andes of Antofagasta, Chile.

The pre-Andes water in the region of Antofagasta is the main drinking and irrigation water source for approximately 3000 Atacameña (indigenous) people. The concentration for soluble elements (filtration in field through a 0.45-microm filter) was: Cd < 0.1 ng/ml; Pb < 0.5 ng/ml; and Zn and Cu between 1 and 10 ng/ml. In particulate material the concentrations were: for Cd < 0.1 ng/ml; for Pb < 0.3 ng/ml; and for Zn and Cu less than 1 ng/ml. The total content of these elements is far below the international recommendations (WHO) and the national standards (N. Ch. 1333 mod. 1987 and 409-1 of 1984). On the other hand, in some rivers a very high arsenic concentration was found (up to 3000 ng/ml) which exceed more than 50 times the national standard. In order to verify the analytical results, inter-laboratory and comparison with different determination methods have been done.

Chile↗

A Dicubane-Like Tetrameric Nickel(II) Azido Complex.

A combination of azido and dipyridylketone (dpk) ligands led to the isolation of the tetranuclear Ni(II) complex 1 (dpkOH and dpkOCH(3) result from solvolysis of dpk). The complex exhibits ferromagnetic behavior, and its structure can be described as a dicubane unit with two missing vertices (see picture).

Journal Article↗

[Subacute thrombosis with antiplatelet treatment in a non-selected population of intracoronary stents: incidence and predictors].

INTRODUCTION: After coronary stenting, the incidence of subacute stent thrombosis have been reduced to 0% using aspirin and ticlopidine, in studies with selected populations and intracoronary ultrasounds. OBJECTIVE: To evaluate the incidence and predictors of subacute stent thrombosis in a nonselected population, using antithrombotic therapy. METHODS: We studied 285 stents, consecutively and successfully implanted in 268 lesions of 226 patients. We used high pressure balloon inflation without intracoronary ultrasound. Post-stenting protocol included aspirin and ticlopidine during four weeks with no anticoagulation. We defined subacute stent thrombosis as death, acute myocardial infarction myocardial infarction or angiographic occlusion of stent, with TIMI flow 0-1, after the first 24 hours and during the first month. RESULTS: Four patients presented events (1.7%): Three nonfatal myocardial infarction after discharge, with documented angiographic thrombosis of stent, and one death due to in-hospital myocardial infarction. All three non-fatal AMI, occurred in vessels less than 3 mm (p = 0.07) and in patients taking aspirin without ticlopidine (p < 0.001). After discharge, three (17%) of 18 patients with inadvertent discontinuation of ticlopidine presented subacute stent thrombosis, in contrast to none of 25 patients taking ticlopidine without aspirin. Excluded patients with discontinuation of ticlopidine, the incidence of subacute stent thrombosis was 0.5%. CONCLUSION: After intracoronary stenting in a nonselected population, using antithrombotic treatment with aspirin and ticlopidine, we may expect a rate of subacute stent thrombosis about 1%. Ticlopidine seems to have the main role in preventing subacute stent thrombosis, above all in predisposing circumstances as small vessels.

Acute Disease↗

Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and[3H]rolipram binding autoradiography. Comparison with monkey and rat brain.

We have examined the distribution of four different cyclic AMP-specific phosphodiesterase isozyme (PDE4A, PDE4B, PDE4C and PDE4D) mRNAs in the brain of different species by in situ hybridization histochemistry and by autoradiography with [3H]rolipram. We have compared the localization of each isozyme in human brain with that in rat and monkey brain. We have found that the four PDE4 isoforms display a differential expression pattern at both regional and cellular level in the three species. PDE4A, PDE4B and PDE4D are widely distributed in human brain, with the two latter appearing more abundant. In contrast, PDE4C in human brain, presents a more restricted distribution, limited to cortex, some thalamic nuclei and cerebellum. This is at variance with the distribution of PDE4C in rat brain, where it is found exclusively in olfactory bulb. In monkey brain, the highest expression for this isoform is found in the claustrum, and at lower levels in cortical areas and cerebellum. PDE4B presented a broad distribution, being expressed in both neuronal and non neuronal cell populations. In general, the distribution of binding sites visualized with [3H]rolipram correlated well with the expression of each PDE4 isozyme.

3',5'-Cyclic-AMP Phosphodiesterases↗

Flip and flop variants of AMPA receptor subunits in the human cerebellum: implication for the selective vulnerability of Purkinje cells.

We investigated the distribution of messenger RNAs coding for flip and flop splice variants ofAMPA receptor subunits in the human cerebellum to determine the relevance of AMPA receptors in the selective vulnerability of Purkinje cells to ischemia. Purkinje cells more abundantly expressed transcripts for flip variant of GluR-A, GluR-C, and GluR-D than granule cells, whereas transcripts for flop variants and GluR-B flip were expressed at similar levels on Purkinje cells and granule cells. These results suggest that human Purkinje cells possess AMPA receptors of the slowly desensitizing class as compared to granule cells. This differential distribution may explain the selective vulnerability of Purkinje cells.

Cell Death↗

Displacement of the binding of 5-HT(1A) receptor ligands to pre- and postsynaptic receptors by (-)pindolol. A comparative study in rodent, primate and human brain.

Using receptor autoradiography we examined the displacement of the binding of [(3)H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and [(3)H][N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cy clohexanecarboxamide. 3HCl] (WAY 100635) to 5-HT(1A) receptors by (-)pindolol in the brain of four different species, rat, guinea pig, monkey and human. (-)Pindolol completely displaced the binding of both tritiated ligands at 10(-6) M in all species and regions examined. The affinity of (-)pindolol for presynaptic 5-HT(1A) receptors in the dorsal raphe nucleus was similar to that observed in postsynaptic locations, such as hippocampus (areas CA1, CA3 and dentate gyrus) or entorhinal cortex. Affinity values (K(i)) were in the range 3.8 - 15.9 nM for [(3)H]8-OH-DPAT and 5.8 - 22.3 nM for [(3)H]WAY 100635. In human brain, the K(i) values using [(3)H]8-OH-DPAT as ligand were 10.8 nM in the dorsal raphe nucleus and 6.5 - 13.5 in postsynaptic sites. The present data do not support the hypothesis that (-)pindolol may displace 5-HT(1A) ligands preferentially from presynaptic 5-HT(1A) receptors in the dorsal raphe nucleus, as suggested by electrophysiological evidence. The affinity of (-)pindolol for human 5-HT(1A) receptors is below the mean plasma concentration attained in depressed patients treated with a combination of fluoxetine and pindolol, which indirectly supports an action of pindolol at 5-HT(1A) receptors in these patients.

Adrenergic beta-Antagonists↗