Reactive Nitrogen Species in Brain after In Vivo Exposure to Arsenic

Arsenic (As) is a natural pollutant, which exposure is related to avariety of diseases like hypertension, diabetes, cancer andneurodegenerative or neurodevelopment impairment but, the exactmechanism by which As exposure could be toxic is still unclear.Studies employing different models of Astoxicity suggested that Ascould cause ROS generation and antioxidant depletion in biologicalsystems, including controversial data related to RNS generation andnitrosative damage. The hypothesis of the present work is that acute Asexposure could trigger an imbalance in the production of RNS in brain,leading to nitrosative stress and nitrosative-dependent cellular damage.The effect of in vivo exposure to As was studied by histopathology ofthe tissue, NO2- plus NO3- content, NO generation rate employingElectron Paramagnetic Resonance (EPR) techniques, and the content ofnitrotyrosine (NO2-Tyr) of total proteins in rat brain by western blottechniques. The data presented here suggested that the exposure to Asincreased the production of NO and lipid radicals in brain, leading tonitrosative damage to proteins and a depletion of the hippocampalpyramidal cell layer, that could affect functionality of the brain.Fil: Bonetto, Julián Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires; ArgentinaFil: Puntarulo, Susana Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentin

Factoring in a Dissipative Quantum Computer

We describe an array of quantum gates implementing Shor's algorithm for prime factorization in a quantum computer. The array includes a circuit for modular exponentiation with several subcomponents (such as controlled multipliers, adders, etc) which are described in terms of elementary Toffoli gates. We present a simple analysis of the impact of losses and decoherence on the performance of this quantum factoring circuit. For that purpose, we simulate a quantum computer which is running the program to factor N = 15 while interacting with a dissipative environment. As a consequence of this interaction randomly selected qubits may spontaneously decay. Using the results of our numerical simulations we analyze the efficiency of some simple error correction techniques.Comment: plain tex, 18 pages, 8 postscript figure

Cotinine participation in chronic nicotinic withdrawal syndrome in rats (Preliminary study)

Numerosos datos clínicos y experimentales han demostrado que la nicotina del tabaco (NI) es la razón de la adicción al tabaco en los seres humanos, a través de la inducción de la tolerancia y la dependencia física. El humo del tabaco contiene otros alcaloides que pueden contribuir a la adicción, como la cotinina (COT). En este estudio se evaluaron los posibles efectos de la COT en ratas durante el síndrome de abstinencia nicotínica midiendo la actividad locomotora espontánea (ALE) utilizando el test del campo abierto. El estudio se llevó a cabo con dos grupos de ratas que recibieron NI 10 mg / kg / día en agua potable durante 120 días (grupos A y B). Luego, en el grupo A, se sustituyó NI por agua potable y en el grupo B, sustituido por COT 12 mg / kg, durante 24 horas en ambos grupos. La actividad locomotora espontánea se registró al final del día 120 (nivel basal) y al final del día 121, al final del período de abstinencia. Los resultados obtenidos se compararon con las mediciones basales. El grupo A mostró diferencias significativas en 3 de los 9 movimientos medidos y el grupo B mostró diferencias significativas en 7 de los 9 movimientos medidos. Cuando el grupo A se comparó con el grupo B sólo 1 movimiento mostró diferencia significativa. Estos resultados sugieren que en la administración crónica de nicotina y en estas condiciones experimentales, la cotinina participa en el síndrome de abstinencia nicotínica.A large amount of clinical and experimental data has shown that tobacco nicotine (NI) is the reason for tobacco addiction in humans, through the induction of tolerance and physical dependence. Tobacco smoke contains other alkaloids that may contribute to addiction, such as cotinine (COT). In this study we evaluated the possible effects of COT in rats during NI abstinence syndrome by measuring spontaneous locomotor activity (SLA) with an open field test. The study was carried out with two groups of rats receiving NI 10 mg / kg / day in drinking water for 120 days (groups A and B). Then, in group A, NI was replaced by drinking water and in group B, substituted by COT, 12 mg / kg, for 24 hours in both groups. Spontaneous locomotor activity was recorded at the end of day 120 (baseline) and at the end of day 121, the end of the abstinence period. The results obtained were compared against the baseline measurements and group A showed significant differences in 3 of the 9 movements measured and group B displayed significant differences in 7 of the 9 movements measured. When group A was compared with Group B only 1 movement showed any significant differences. These results suggest that cotinine participates in the nicotine withdrawal syndrome in chronic nicotine administration under these experimental conditions.Fil: Sassone, Adriana Haydée. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Sanidad Nutrición Bromatología y Toxicología; ArgentinaFil: Merini, Luciano Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Sanidad Nutrición Bromatología y Toxicología; ArgentinaFil: Quiroga, Patricia Noemí. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Sanidad Nutrición Bromatología y Toxicología; ArgentinaFil: Sarchi, María I.. Universidad de Buenos Aires; ArgentinaFil: Lopez, Clara M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Sanidad Nutrición Bromatología y Toxicología; ArgentinaFil: Roses, Otmaro Enrique. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Sanidad Nutrición Bromatología y Toxicología; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Sanidad Nutrición Bromatología y Toxicología; Argentin

Menhaden oil rich diet and experimental renal damage due to ischemia reperfusion

Renal necrosis can be induced in weanling rats due to choline deficient diet. Menhaden oil has a protective effect against the development of renal necrosis in choline deficient weanling rats. The aim of this work was to determine the effects of menhaden oil in a model of acute kidney injury due to ischemia reperfusion. Wistar rats were divided into two groups and fed vegetable oils or menhaden oil as lipids. Unilateral renal ischemia was performed for 30 minutes and animals were sacrificed 48 hours later. Histopathological examination showed no significant differences between groups. Menhaden oil did not prevent histopathological lesions.Fil: Ossani, Georgina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Marcotegui, Ariel R.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Uceda, Ana Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Monserrat, Alberto Juan. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Lago, Néstor Rubén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentin

Sub-chronic iron overload triggers oxidative stress development in rat brain: Implications for cell protection

This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR•)/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A•)/ascorbate (AH-) content ratio and the oxidation rate of 2′,7′-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation.Fil: Piloni, Natacha Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fernandez, Virginia. Universidad de Chile; ChileFil: Videla, Luis A.. Universidad de Chile; ChileFil: Puntarulo, Susana Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentin

Reyes's syndrome, encephalopathy, hyperammonemia and acetyl salicylic acid ingestion in a city hospital of Buenos Aires, Argentina

Twelve cases of Reye's syndrome are presented with different degrees of encephalopathy, hyperammonemia and hypoglycemia; associated to acetyl salicylic acid (ASA) ingestion. The aim of the present retrospective study was to describe our experience in selected patients with Reye's syndrome associated to the ASA ingestion and to underline the influence of hyperammonemia on Reye's encephalopathy. All the cases presented moderate hyperbilirubinemia, elevated alanine aminotransferase, aspartate aminotransferase with an average of 302±205 UI/L and 285±149 UI/L respectively. Arterial blood ammonia averaged 172.4±71.3 μmol/L and glycaemia averaged 35.2±17.0 mg/ dl. A high mortality was found in our series (41.7%). Considering that encephalopathy is the leading syndrome in these cases, the influence of ammonia on brain tissue was described. Glutamate is an excitotoxic neurotransmitter, capable to produce neuron and astrocyte damage and apoptosis. The presence of ASA could cause the onset of the mitochondrial permeability transition and the mitochondrial swelling in the astrocyte, leading to hyperammonemia. In Reye's syndrome, hyperammonemia and perhaps the increase of glutamate are the leading factors in the mechanism of brain damage and encephalopathy. Aspirin must be carefully administrated and controlled by professionals. Furthermore, parents must be informed about the risks in the use of this drug in children.Fil: Lemberg, Abraham. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fernández, María A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Coll, Carlos. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rosello, Diego O.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Romay, Salvador. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Filinger, Ester Julia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Pharmacological targeting of histamine H4 receptor in periodontal disease

Objective: The objective of this study was to investigate whether histamine H4 receptor (H4R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva. Methods: Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated. Results: The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters. Conclusions: H4 receptor antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4R could be an attractive strategy to improve periodontal health.Fil: Prestifilippo, J. P.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Fernández Solari, José Javier. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rios, Carlos Ezequiel. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mohn, Claudia Ester. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rivera, E. S.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Elverdin, J. C.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Medina, Vanina Araceli. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Changes in CNS cells in Hyperammonemic portal hypertensive rats

Rats with pre-hepatic portal hypertension because of partial portal vein ligation develop minimal hepatic encephalopathy (MHE) with hyperammonemia, impaired blood–brain barrier, mild brain edema, and severe mitochondrial changes in the hippocampus. The aim of this study was to evaluate changes of different neural cells in the cerebral cortex and the hippocampus. Animals were divided into two groups, MHE and sham. Astrocytes were studied by immunostaining with glial fibrillary acidic protein and S100β protein; neurons were immunostained with neuronal nuclear marker, microtubule associated protein-2, and NF-200 and capillaries with Nestin. The hypoxia-inducible factor 1α (HIF-1α) and its downstream proteins, P-glycoprotein (P-gp) and erythropoietin receptor (Epo-R), were also evaluated. Astrocytes were increased in area and number only in the hippocampus, while S100β increased in both brain areas in MHE animals. Microtubule associated protein-2 and NF-200 immunoreactivities (-ir) were significantly reduced in both areas. Hippocampal Nestin-ir was increased in MHE animals. These cellular changes were similar to those described in ischemic conditions, thus HIF-1α, P-gp, and Epo-R were also evaluated. A high expression of HIF-1α in cortical neurons was observed in the MHE group. It is likely that this hypoxia-like state is triggered via ammonia occupying the binding domain of HIF-1α and thereby preventing its degradation and inducing its stabilization, leading to the over-expression of P-gp and the Epo-R.Fil: Tallis, Silvina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Souto, Pablo A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Delfante, Amalia E.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin