Publications by authors named "Repetto M"

210 Publications

Systematic T1 improvement for hyperpolarized 129xenon.

J Magn Reson 2015 Mar 31;252:163-9. Epub 2015 Jan 31.

Institute of Physics, Johannes Gutenberg University, Staudingerweg 7, 55128 Mainz, Germany.

The spin-lattice relaxation time T1 of hyperpolarized (HP)-(129)Xe was improved at typical storage conditions (i.e. low and homogeneous magnetic fields). Very long wall relaxation times T(1)(wall) of about 18 h were observed in uncoated, spherical GE180 glass cells of ∅=10 cm which were free of rubidium and not permanently sealed but attached to a standard glass stopcock. An "aging" process of the wall relaxation was identified by repeating measurements on the same cell. This effect could be easily removed by repeating the initial cleaning procedure. In this way, a constant wall relaxation was ensured. The Xe nuclear spin-relaxation rate 1/T1(Xe-Xe) due to van der Waals molecules was investigated too, by admixing three different buffer gases (N(2), SF(6) and CO(2)). Especially CO(2) exhibited an unexpected high efficiency (r) in shortening the lifetime of the Xe-Xe dimers and hence prolonging the total T1 relaxation even further. These measurements also yielded an improved accuracy for the van der Waals relaxation for pure Xe (with 85% (129)Xe) of T(1)(Xe-Xe)=(4.6±0.1)h. Repeating the measurements with HP (129)Xe in natural abundance in mixtures with SF6, a strong dependence of T(1)(Xe-Xe) and r on the isotopic enrichment was observed, uncovering a shorter T(1)(Xe-Xe) relaxation for the (129)Xe in natural composition as compared to the 85% isotopically enriched gas.
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http://dx.doi.org/10.1016/j.jmr.2015.01.015DOI Listing
March 2015

Brain antioxidant responses to acute iron and copper intoxications in rats.

Metallomics 2014 Nov;6(11):2083-9

Department of General and Inorganic Chemistry, University of Buenos Aires, Buenos Aires, Argentina.

Dose- and time-dependent antioxidant responses to Fe (0-60 mg kg(-1)) and Cu overloads (0-30 mg kg(-1)) in rat brains are described by the C50 and the t1/2, the brain metal concentration and the time for half maximal oxidative responses. Brain GSH and the GSH/GSSG ratio markedly decreased after Fe and Cu treatments (50-80%) with a t1/2 of 9-10 h for GSH and of 4 h for GSH/GSSG for both metals. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease of GSH and the increase of in vivo chemiluminescence had similar time courses. The C50 for brain chemiluminescence, GSH and hydrophilic and lipophilic antioxidants were in similar ranges (32-36 μg Fe g(-1) brain and 10-18 μg Cu g(-1) brain), which indicated a unique free-radical mediated process for each metal. The brain concentration of hydrophilic and lipophilic antioxidants decreased after Fe and Cu loads; hydrophilic antioxidants decreased by 46-68% with a t1/2 of 10-11 h and lipophilic antioxidants decreased by 75-45% with a t1/2 of 10-12 h. Cu,Zn-SOD and CAT activities and the protein expression were adaptively increased (100-90% after Fe and Cu loads), with a t1/2 of 8-12 h. GPx-4 activity decreased after both metal loads by 73-27% with a t1/2 of 8-4 h with decreased protein expression.
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http://dx.doi.org/10.1039/c4mt00159aDOI Listing
November 2014

Rat liver antioxidant response to iron and copper overloads.

J Inorg Biochem 2014 Aug 30;137:94-100. Epub 2014 Apr 30.

Department of General and Inorganic Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina. Electronic address:

The rat liver antioxidant response to Fe and Cu overloads (0-60mg/kg) was studied. Dose- and time-responses were determined and summarized by t1/2 and C50, the time and the liver metal content for half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58-66%) and Cu (79-81%) loads, with t1/2 of 4.0 and 2.0h. The C50 were in a similar range for all the indicators (110-124μgFe/g and 40-50μgCu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60-75%; t1/2: 4.5 and 4.0h). Lipophilic antioxidants were also decreased (30-92%; t1/2: 7.0 and 5.5h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t1/2: 8-8.5h and Mn-SOD: t1/2: 8.5-8.0h). Catalase activity was increased after Fe (65%; t1/2: 8.5h) and decreased after Cu (26%; t1/2: 8.0h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22-39% with a t1/2 of 4.5h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol (SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads.
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http://dx.doi.org/10.1016/j.jinorgbio.2014.04.014DOI Listing
August 2014

Oxidative damage to rat brain in iron and copper overloads.

Metallomics 2014 Aug;6(8):1410-6

Department of General and Inorganic Chemistry, University of Buenos Aires, Buenos Aires, Argentina.

This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.
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http://dx.doi.org/10.1039/c3mt00378gDOI Listing
August 2014

Skin and proximity effects in the conductors of split gradient coils for a hybrid Linac-MRI scanner.

J Magn Reson 2014 May 12;242:86-94. Epub 2014 Feb 12.

School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

In magnetic resonance imaging (MRI), rapidly changing gradient fields are applied to encode the magnetic resonance signal with spatial position; however eddy currents are induced in the surrounding conducting structures depending on the geometry of the conductor and the excitation waveform. These alternating fields change the spatial profile of the current density within the coil track with the applied frequencies of the input waveform and by their proximity to other conductors. In this paper, the impact of the conductor width and the excited frequency over the parameters that characterise the performance of split transverse and longitudinal gradient coils are studied. Thirty x-gradient coils were designed using a "free-surface" coil design method and the track width was varied from 1mm to 30mm with an increment value of 1mm; a frequency sweep analysis in the range of 100Hz to 10kHz was performed using the multi-layer integral method (MIM) and parameters such as power loss produced by the coil and generated in the cryostat, inductance, coil efficiency (field strength/operating current), magnetic field profile produced by the coil and the eddy currents were studied. An experimental validation of the theoretical model was performed on an example coil. Coils with filamentary conductor segments were also studied to compare the simulated parameters with those produced by coils with a finite track. There was found to be a significant difference between the parameters calculated using filamentary coils and those obtained when the coil is simulated using finite size tracks. A wider track width produces coil with superior efficiency and low resistance; however, due to the skin effect, the power loss increases faster in wider tracks than in those generated in coils with narrow tracks. It was demonstrated that rapidly changing current paths must be avoided in order to mitigate the power loss and the spatial asymmetry in the current density profile. The decision of using narrow or wider tracks in split coils should be carefully investigated using a temperature analysis which includes skin and proximity effects.
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http://dx.doi.org/10.1016/j.jmr.2014.02.002DOI Listing
May 2014

Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.

Neurologia 2014 Nov-Dec;29(9):567-72. Epub 2013 Oct 18.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular (IBIMOL, UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.

Introduction: Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear.

Development: Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations.

Conclusions: Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment.
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http://dx.doi.org/10.1016/j.nrl.2013.05.006DOI Listing
August 2015

Multilayer integral method for simulation of eddy currents in thin volumes of arbitrary geometry produced by MRI gradient coils.

Magn Reson Med 2014 May 1;71(5):1912-22. Epub 2013 Jul 1.

The School of Information Technology and Electrical Engineering, The University of Queensland, Australia.

Purpose: This article aims to present a fast, efficient and accurate multi-layer integral method (MIM) for the evaluation of complex spatiotemporal eddy currents in nonmagnetic and thin volumes of irregular geometries induced by arbitrary arrangements of gradient coils.

Methods: The volume of interest is divided into a number of layers, wherein the thickness of each layer is assumed to be smaller than the skin depth and where one of the linear dimensions is much smaller than the remaining two dimensions. The diffusion equation of the current density is solved both in time-harmonic and transient domain.

Results: The experimentally measured magnetic fields produced by the coil and the induced eddy currents as well as the corresponding time-decay constants were in close agreement with the results produced by the MIM. Relevant parameters such as power loss and force induced by the eddy currents in a split cryostat were simulated using the MIM.

Conclusion: The proposed method is capable of accurately simulating the current diffusion process inside thin volumes, such as the magnet cryostat. The method permits the priori-calculation of optimal pre-emphasis parameters. The MIM enables unified designs of gradient coil-magnet structures for an optimal mitigation of deleterious eddy current effects.
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http://dx.doi.org/10.1002/mrm.24819DOI Listing
May 2014

The oxidative stress induced in vivo by Shiga toxin-2 contributes to the pathogenicity of haemolytic uraemic syndrome.

Clin Exp Immunol 2013 Sep;173(3):463-72

Servicio de Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS 'Dr Carlos G. Malbrán', Buenos Aires, Argentina.

Typical haemolytic uraemic syndrome (HUS) is caused by Shiga toxin (Stx)-producing Escherichia coli infections and is characterized by thrombotic microangiopathy that leads to haemolytic anaemia, thrombocytopenia and acute renal failure. Renal or neurological sequelae are consequences of irreversible tissue damage during the acute phase. Stx toxicity and the acute inflammatory response raised by the host determine the development of HUS. At present there is no specific therapy to control Stx damage. The pathogenic role of reactive oxygen species (ROS) on endothelial injury has been largely documented. In this study, we investigated the in-vivo effects of Stx on the oxidative balance and its contribution to the development of HUS in mice. In addition, we analysed the effect of anti-oxidant agents as therapeutic tools to counteract Stx toxicity. We demonstrated that Stx induced an oxidative imbalance, evidenced by renal glutathione depletion and increased lipid membrane peroxidation. The increased ROS production by neutrophils may be one of the major sources of oxidative stress during Stx intoxication. All these parameters were ameliorated by anti-oxidants reducing platelet activation, renal damage and increasing survival. To conclude, Stx generates a pro-oxidative state that contributes to kidney failure, and exogenous anti-oxidants could be beneficial to counteract this pathogenic pathway.
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http://dx.doi.org/10.1111/cei.12124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949634PMC
September 2013

The protective effect of menhaden oil in the oxidative damage and renal necrosis due to dietary choline deficiency.

Food Funct 2013 Feb 12;4(3):448-52. Epub 2012 Dec 12.

Centre of Experimental Pathology, Faculty of Medicine, University of Buenos Aires, JE Uriburu 950, Buenos Aires, Argentina.

Weanling rats fed a choline-deficient diet develop kidney oxidative damage, tubular and cortical kidney necrosis, renal failure and animal death. The effect of dietary menhaden oil was assayed on the mentioned sequence correlating oxidative stress with renal structure and function. Rats were fed ad libitum 4 different diets: (a) a choline-deficient diet with corn oil and sunflower hydrogenated oil as a source of fatty acids; (b) the same diet supplemented with choline; (c) a choline-deficient diet with menhaden oil as a source of fatty acids; and (d) the previous diet supplemented with choline. Animals were sacrificed at days 0, 2, 4 and 7. The histopathological study of the kidneys showed that renal necrosis was only observed at day 7 in choline-deficient rats receiving the vegetable oil diet, simultaneously with increased creatinine plasma levels. Homogenate chemiluminescence (BOOH-initiated chemiluminescence) and phospholipid oxidation indicate the development of oxidative stress and damage in choline-deficient rats fed vegetable oils as well as the protective effect of menhaden oil. Rats fed with the fish oil diet showed that oxidative stress and damage develop later, as compared with vegetable oil, with no morphological damage during the experimental period.
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http://dx.doi.org/10.1039/c2fo30229bDOI Listing
February 2013

The acute toxicity of iron and copper: biomolecule oxidation and oxidative damage in rat liver.

J Inorg Biochem 2012 Nov 11;116:63-9. Epub 2012 Jul 11.

Institute of Biochemistry and Molecular Medicine (IBIMOL, UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.

The transition metals iron (Fe) and copper (Cu) are needed at low levels for normal health and at higher levels they become toxic for humans and animals. The acute liver toxicity of Fe and Cu was studied in Sprague Dawley male rats (200 g) that received ip 0-60 mg/kg FeCl(2) or 0-30 mg/kg CuSO(4). Dose and time-responses were determined for spontaneous in situ liver chemiluminescence, phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants. The doses linearly defined the tissue content of both metals. Liver chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with half maximal responses at contents (C(50%)) of 110 μgFe/g and 42 μgCu/g liver, and with half maximal time responses (t(1/2)) of 4h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C(50%) of 118 μg Fe/g and 45 μg Cu/g and with t(1/2) of 7h and 8h. Protein oxidation increased 1.6 times for Fe with C(50%) at 113 μg Fe/g and 1.2 times for Cu with 50 μg Cu/g and t(1/2) of 4h and 5h respectively. The accumulation of Fe and Cu in liver enhanced the rate of free radical reactions and produced oxidative damage. A similar free radical-mediated process, through the formation HO(•) and RO(•) by a Fenton-like homolytic scission of H(2)O(2) and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.
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http://dx.doi.org/10.1016/j.jinorgbio.2012.07.004DOI Listing
November 2012

Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

Diabetes Res Clin Pract 2012 Oct 2;98(1):68-74. Epub 2012 Jun 2.

Sirio-Libanés Hospital, Department of Neurology, School of Medicine, University of Buenos Aires (UBA), Buenos Aires, Argentina.

Aim: To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis.

Methods: The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects.

Results: The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients.

Conclusions: In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores.
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http://dx.doi.org/10.1016/j.diabres.2012.05.013DOI Listing
October 2012

Effects of GABAB receptor agonists and antagonists on glycemia regulation in mice.

Eur J Pharmacol 2012 Feb 21;677(1-3):188-96. Epub 2011 Dec 21.

Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.

γ-Aminobutyric acid (GABA) inhibits insulin secretion through GABA(B) receptors in pancreatic β-cells. We investigated whether GABA(B) receptors participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABA(B) receptor agonist baclofen (7.5mg/kg, i.p.) presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT, 2g/kg body weight, i.p.). The GABA(B) receptor antagonist 2-hydroxysaclofen (15 mg/kg, i.p.) improved the GTT and reversed the baclofen effect. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In incubated islets 1.10(-5)M baclofen inhibited 20mM glucose-induced insulin secretion and this effect was reversed by coincubation with 1.10(-5)M 2-hydroxysaclofen. In chronically-treated animals (18 days) both the receptor agonist (5mg/kg/day i.p.) and the receptor antagonist (10mg/kg/day i.p.) induced impaired GTTs; the receptor antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests, body weight and food intake were observed with the treatments. In addition glucagon, insulin-like growth factor I, prolactin, corticosterone and growth hormone, other hormones involved in glucose metabolism regulation, were not affected by chronic baclofen or 2-hydroxysaclofen. In islets obtained from chronically injected animals with baclofen, 2-hydroxysaclofen or saline (as above), GABA(B2) mRNA expression was not altered. Results demonstrate that GABA(B) receptors are involved in the regulation of glucose homeostasis in vivo. Treatment with receptor agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.
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http://dx.doi.org/10.1016/j.ejphar.2011.12.013DOI Listing
February 2012

[Vertigo and vertical nystagmus associated with intrathecal morphine administration and resolution by naloxone].

Medicina (B Aires) 2011 ;71(5):457-8

Servicio de Clínica Médica, Sanatorio Otamendi y Miroli, Buenos Aires.

Combined regional anesthesia is frequently used as a tool for management of postoperative pain. The profile of side effects of the opioids used via this route is similar to those occurring after systemic administration. The onset of vertigo with vertical nystagmus is an adverse effect rarely described after the use of intrathecal, epidural or intravenous morphine. We report the case of a patient who presented this complication in the postoperative period of a partial nephrectomy, after the administration of intrathecal morphine, with complete resolution by intravenous naloxone.
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August 2012

[Postpartum cerebral venous sinus thrombosis].

Medicina (B Aires) 2011 ;71(4):380

Servicio de Clínica Médica, Sanatorio Otamendi y Miroli, Buenos Aires, Argentina.

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June 2012

Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

Appl Radiat Isot 2011 Dec 2;69(12):1676-9. Epub 2011 Mar 2.

Gerencia de Investigación y Aplicaciones, Comisión Nacional de Energía Atómica, Argentina.

Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes.
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http://dx.doi.org/10.1016/j.apradiso.2011.02.020DOI Listing
December 2011

Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

Appl Radiat Isot 2011 Dec 15;69(12):1672-5. Epub 2011 Feb 15.

Gerencia de Investigación y Aplicaciones, Comisión Nacional de Energía Atómica, San Martin, Buenos Aires, Argentina.

We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas.
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http://dx.doi.org/10.1016/j.apradiso.2011.01.040DOI Listing
December 2011

Effects of rotenone and pyridaben on complex I electron transfer and on mitochondrial nitric oxide synthase functional activity.

J Bioenerg Biomembr 2010 Oct 1;42(5):405-12. Epub 2010 Oct 1.

Department of Biochemistry and Molecular Biology, School of Medicine, University of Cádiz, Plaza Fragela 9, 11003 Cádiz, Spain.

Rotenone and pyridaben were tested on activities and properties of rat brain mitochondria determining Ki (inhibitor concentration at half maximal inhibition) and Imax (% of inhibition at maximal inhibitor concentration). The assayed activities were complexes I, II and IV, respiration in states 3, 3u (uncoupled) and 4, biochemical and functional activities of mitochondrial nitric oxide synthase (mtNOS), and inner membrane potential. Selective inhibitions of complex I activity, mitochondrial respiration and membrane potential with malate-glutamate as substrate were observed, with a Ki of 0.28-0.36 nmol inhibitor/mg of mitochondrial protein. Functional mtNOS activity was half-inhibited at 0.70-0.74 nmol inhibitor/mg protein in state 3 mitochondria and at 2.52-2.98 nmol inhibitor/mg protein in state 3u mitochondria. This fact is interpreted as an indication of mtNOS being structurally adjacent to complex I with an intermolecular mtNOS-complex I hydrophobic bonding that is stronger at high Δψ and weaker at low Δψ.
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http://dx.doi.org/10.1007/s10863-010-9309-4DOI Listing
October 2010

Bioactivity of sesquiterpenes: compounds that protect from alcohol-induced gastric mucosal lesions and oxidative damage.

Mini Rev Med Chem 2010 Jun;10(7):615-23

Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, Junín 956, C1113AAD Buenos Aires, Argentina.

Sesquiterpene lactones of the guaianolide and eudermanolide types are considered of interest because they have an effect in the regulation and prevention of oxidative damage and inflammation-mediated biological damage. Dehydroleucodine, a natural sesquiterpene isolated from Artemisia douglasiana Besser, and ilicic aldehyde, a semi-synthetic sesquiterpene lactones, showed in vivo protection in ethanol-induced gastric mucosa damage. This action was determined by in situ gastric mucosa chemiluminescence and by tissue antioxidant content.
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http://dx.doi.org/10.2174/138955710791383992DOI Listing
June 2010

The involvement of transition metal ions on iron-dependent lipid peroxidation.

Arch Toxicol 2010 Apr 20;84(4):255-62. Epub 2009 Nov 20.

Laboratory of Free Radical Biology, Department of Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.

The metals iron (Fe) and copper (Cu) are considered trace elements, and the metals cobalt (Co) and nickel (Ni) are known as ultra-trace elements, considering their presence in low to very low quantity in humans. The biologic activity of these transition metals is associated with the presence of unpaired electrons that favor their participation in redox reactions. They are part of important enzymes involved in vital biologic processes. However, these transition metals become toxic to cells when they reach elevated tissue concentrations and produce cellular oxidative damage. Phospholipid liposomes (0.5 mg/ml, phosphatidylcholine (PC)/phosphatidylserine (PS), 60/40) were incubated for 60 min at 37 degrees C with 25 microM of Fe2+ in the absence and in the presence of Cu2+, Co2+, and Ni2+ (0-100 microM) with and without the addition of hydrogen peroxide (H2O2, 5-50 microM). Iron-dependent lipid peroxidation in PC/PS liposomes was assessed by thiobarbituric acid-reactive substances (TBARS) production. Metal transition ions promoted lipid peroxidation by H2O2 decomposition and direct homolysis of endogenous hydroperoxides. The Fe2+-H2O2-mediated lipid peroxidation takes place by a pseudo-second order process, and the Cu2+-mediated process by a pseudo-first order reaction. Co2+ and Ni2+ alone do not induce lipid peroxidation. Nevertheless, when they are combined with Fe2+, Fe2+-H2O2-mediated lipid peroxidation was stimulated in the presence of Ni2+ and was inhibited in the presence of Co2+. The understanding of the effects of transition metal ions on phospholipids is relevant to the prevention of oxidative damage in biologic systems.
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http://dx.doi.org/10.1007/s00204-009-0487-yDOI Listing
April 2010

Oxidative damage: the biochemical mechanism of cellular injury and necrosis in choline deficiency.

Exp Mol Pathol 2010 Feb 12;88(1):143-9. Epub 2009 Nov 12.

Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina.

Oxidative stress and damage are characterized by decreased tissue antioxidant levels, consumption of tissue alpha-tocopherol, and increased lipid peroxidation. These processes occur earlier than necrosis in the liver, heart, kidney, and brain of weanling rats fed a choline deficient (CD) diet. In tissues, water-soluble antioxidants were analyzed as total reactive antioxidant potential (TRAP), alpha-tocopherol content was estimated from homogenate chemiluminescence (homogenate-CL), and lipid peroxidation was evaluated by thiobarbituric acid reactive substances (TBARS). Histopathology showed hepatic steatosis at days 1-7, tubular and glomerular necrosis in kidney at days 6 and 7, and inflammation and necrosis in heart at days 6 and 7. TRAP levels decreased by 18%, 48%, 56%, and 66% at day 7, with t(1/2) (times for half maximal change) of 2.0, 1.8, 2.5, and 3.0 days in liver, kidney, heart, and brain, respectively. Homogenate-CL increased by 97%, 113%, 18%, and 297% at day 7, with t(1/2) of 2.5, 2.6, 2.8, and 3.2 days in the four organs, respectively. TBARS contents increased by 98%, 157%, 104%, and 347% at day 7, with t(1/2) of 2.6, 2.8, 3.0, and 5.0 days in the four organs, respectively. Plasma showed a 33% decrease in TRAP and a 5-fold increase in TBARS at day 5. Oxidative stress and damage are processes occurring earlier than necrosis in the kidney and heart. In case of steatosis prior to antioxidant consumption and increased lipid peroxidation, no necrosis is observed in the liver.
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http://dx.doi.org/10.1016/j.yexmp.2009.11.002DOI Listing
February 2010

[Carotidynia ].

Medicina (B Aires) 2009 ;69(4):458

Servicio de Clínica Médica, Sanatorio Otamendi y Miroli, Buenos Aires.

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October 2010

Development of a tandem-electrostatic-quadrupole accelerator facility for BNCT.

Appl Radiat Isot 2009 Jul 27;67(7-8 Suppl):S266-9. Epub 2009 Mar 27.

Departamento de Física, Comisión Nacional de Energía Atómica, Av. Gral Paz 1499 (1650), San Martín, Buenos Aires, Argentina.

In this work we describe the present status of an ongoing project to develop a tandem-electrostatic-quadrupole (TESQ) accelerator facility for accelerator-based (AB) BNCT at the Atomic Energy Commission of Argentina in Buenos Aires. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the (7)Li(p,n)(7)Be reaction slightly beyond its resonance at 2.25 MeV. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the (7)Li(p,n)(7)Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. An electrostatic machine is the technologically simplest and cheapest solution for optimized AB-BNCT. The machine being designed and constructed is a folded TESQ with a high-voltage terminal at 1.2 MV intended to work in air. Such a machine is conceptually shown to be capable of transporting and accelerating a 30 mA proton beam to 2.4 MeV. The general geometric layout, its associated electrostatic fields, and the acceleration tube are simulated using a 3D finite element procedure. The design and construction of the ESQ modules is discussed and their electrostatic fields are investigated. Beam transport calculations through the accelerator are briefly mentioned. Likewise, work related to neutron production targets, strippers, beam shaping assembly and patient treatment room is briefly described.
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http://dx.doi.org/10.1016/j.apradiso.2009.03.084DOI Listing
July 2009

Differentiation of Spanish brandies according to their metal content.

Talanta 2001 Mar;54(1):53-9

Departamento de Bioquimica, Bromatologia, Toxicologia y Medicina Legal, Universidad de Sevilla, 41012 Sevilla, Spain.

Eleven metals, namely, aluminium, calcium, cadmium, copper, iron, lead, magnesium, manganese, potassium, sodium and zinc were determined in twenty samples of Sherry brandies and twelve samples of Penedés brandies by applying atomic spectrometry techniques. Flame atomic absorption spectrometry was used for quantitating calcium, copper, iron, magnesium, manganese and zinc; atomic emission spectrometry to determine potassium and sodium; and graphite furnace atomic absorption spectrometry to analyse aluminium, cadmium and lead. A chemometric approach was followed to study the discrimination between brandies from Sherry or Penedés according to the metal profile.
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http://dx.doi.org/10.1016/s0039-9140(00)00623-8DOI Listing
March 2001

Psychopharmacology in HIV-infected patients.

Psychosom Med 2008 Jun 2;70(5):585-92. Epub 2008 Jun 2.

Department of Psychiatry, Provena Covenant Medical Center, Champaign, Illinois 61820, USA.

Neuropsychiatric disorders and syndromes may be underdiagnosed and inadequately treated in individuals infected with HIV. Depression in particular is among the most prevalent diagnoses, and data from controlled clinical studies have shown that antidepressant medications are efficacious and safe for treating depression in HIV-infected persons. A significant shortcoming of this literature is that most of the available data are from studies conducted before the advent of highly active antiretroviral therapy. In addition, apart from antidepressant medications, controlled studies systematically assessing efficacy and safety issues for other classes of psychotropic drugs (e.g., antipsychotic and anxiolytic medications) in HIV-infected persons are lacking. This review summarizes essential findings pertaining to the use of psychotropic medications to treat depression and other neuropsychiatric disorders in the context of HIV. It includes a discussion of clinically relevant treatment considerations (e.g., side effects, drug-drug interactions) derived from the existing literature as well as judgments that clinicians face in the absence of research data. Despite some shortcomings of the existing literature, overall there is compelling evidence that the appropriate use of psychotropic medications (coupled with behavioral therapy) can improve the quality of life of mentally ill HIV-infected individuals.
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http://dx.doi.org/10.1097/PSY.0b013e3181777190DOI Listing
June 2008

Insulin, glucose and glycated hemoglobin in Alzheimer's and vascular dementia with and without superimposed Type II diabetes mellitus condition.

J Neural Transm (Vienna) 2008 30;115(1):77-84. Epub 2007 Aug 30.

Facultad de Medicina, Hospital Sirio-Libanés, UBA, FACENE, Buenos Aires, Argentina.

Increased concentrations of insulin, glucose and glycohemoglobin are associated with Type II diabetes mellitus (DM) and recognized as characteristic markers of the disease; in Alzheimer's (AD), Vascular dementia (VaD), and both dementia's with superimposed diabetes (AD + DM, VaD + DM) the knowledge is scarce. The sample (n = 122; males = 60; mean age = 73 +/- 7) comprised DM, AD, VaD, AD + DM, and VaD + DM patients, and healthy controls (C). The ANOVA's yielded significant differences between groups: Insulin p = 3.7 x 10(-3); Glucose p < 10(-12); Glycohemoglobin p = 9.2x10(-4). Comparisons between groups (DM vs. C, AD + DM vs. AD, VaD + DM vs. VaD, and demented DM vs. non-demented DM) resulted significant for all variables (Bonferroni's statistic, alpha = 0.05). Diabetic and diabetic demented patients presented significant increases largely different from controls (0.01 < p < 0.001), unlike the non-significant changes in their non-diabetic counterparts; linear relationships were found across all groups. The correlation's insulin/glucose and insulin/glycohemoglobin change to positive within demented groups, indicating a different performance of insulin in demented and non-demented subjects.
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http://dx.doi.org/10.1007/s00702-007-0804-7DOI Listing
May 2008

Oxidative damage lipid peroxidation in the kidney of choline-deficient rats.

Front Biosci 2007 Jan 1;12:1174-83. Epub 2007 Jan 1.

Centro de Patología Experimental, Departamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.

Phosphatidylcholine is the most abundant phospholipid constituent of cell membranes and choline is a quaternary amine required for phosphatidylcholine synthesis. The impairment of membrane functions is considered as an indication of oxidative damage. In order to kinetically analyze the time course of the pathogenesis of renal necrosis following to choline deficiency in weanling rats, we determined markers of membrane lipid peroxidation (thiobarbituric acid reactive substances; TBARS and hydroperoxide-induced chemiluminescence (BOOH-CL) ) and studied the histopathological damage. Plasma TBARS (t(1/2) = 2.5 days) was an early indicator of systemic oxidative stress, likely involving liver and kidney. The levels of TBARS an BOOH-CL increased by 80% and by 183%, respectively, in kidney homogenates with t(1/2) = 1.5 days and 4 days, respectively. The levels of BOOH-CL were statistically higher in rats fed a choline-deficient diet at day 6, in a mixture of membranes (from plasmatic, smooth and rough endoplasmic reticulum and Golgi), in mitochondrial membranes and in lysosomal membranes. The results indicate that choline deficiency produces oxidative damage in kidney subcellular membranes. Necrosis involved mainly convoluted tubules and appeared with a t(1/2) = 5.5 days. An increase in the production of reactive oxygen species, triggered by NADH overproduction in the mitochondrial dysfunction associated with choline deficiency appears as one of the pathogenic mechanism of mitochondrial and cellular oxidative damage in choline-deficiency.
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http://dx.doi.org/10.2741/2135DOI Listing
January 2007

High concentrations of pralidoxime are needed for the adequate reactivation of human erythrocyte acetylcholinesterase inhibited by dimethoate in vitro.

Toxicol In Vitro 2005 Oct 19;19(7):893-7. Epub 2005 Aug 19.

National Institute of Toxicology and Forensic Sciences, Av. Dr. Fedriani s/n, 41009 Sevilla, Spain.

Due to the current controversy about the real effectiveness of the oximes in the treatment of organophosphate poisoning, the reactivation capacity of pralidoxime has been evaluated in vitro on human erythrocyte acetylcholinesterase inhibited by dimethoate. In the in vitro model, a partial recovery of acetylcholinesterase activity was observed with concentrations from 0.066 mM pralidoxime, probably useful enough to prevent death in most cases in vivo. However, much more effectiveness was observed with concentrations up to 0.70 mM pralidoxime. Although pralidoxime should be applied as soon as possible after organophosphate exposure, the application of the antagonist can be useful even 24h after, particularly for organophosphates with biological half-life longer than one day. The protective capacity of pralidoxime after the application was reduced up to 50% in 6h and disappeared almost completely in 24h. Furthermore, the pesticide and its metabolites remained active and were able to inhibit the enzyme as soon as pralidoxime reduced its antagonist capacity. Our results in conjunction with the short half-life of pralidoxime suggest that the maintenance of higher plasmatic concentrations than the currently used should be considered in the management of severe poisoned patients, although adverse effects could be expected.
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http://dx.doi.org/10.1016/j.tiv.2005.06.024DOI Listing
October 2005

Brain-immune interactions in neuropsychiatry: highlights of the basic science and relevance to pathogenic factors and epiphenomena.

CNS Spectr 2001 May;6(5):383-8, 391

Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL 32610-0256, USA.

Unraveling the significant complexity of brain-immune interactions could provide essential new insights and potential treatment considerations for the clinical neurosciences. Despite considerable research relating immunological changes to major neuropsychiatric disorders, it has been difficult to establish that immunological processes are involved in the development of central nervous system pathology associated with these disorders. This brief article highlights some of the landmark basic studies and seeks to convey essential principles guiding research in brain-immune interactions. Research in this area often incorporates several disciplines, ranging from psychology and neuroscience to immunology and molecular genetics. The clinical implications of this area of research are discussed, with emphasis on the challenge of disentangling pathogenic factors and valid markers of disease from epiphenomena.
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http://dx.doi.org/10.1017/s1092852900021751DOI Listing
May 2001

Resistive index and antihypertensive therapy in kidney transplantation.

Arch Ital Urol Androl 2005 Mar;77(1):54-7

Nephrology, Dialysis and Transplantation Unit, Saint Paul Hospital, Savona, Italy.

Objectives: To investigate in kidney transplanted patients any possible correlation between intrarenal Doppler Resistive Index (RI) and arterial hypertension (AH); to detect any possible angiotensin converting enzime inhibitors (ACE-I)/angiotensin receptor blockers (ARB) influence on RI.

Material And Methods: Our retrospective study took into consideration 80 consecutive renal allograft sonography scans of 54 patients (37 males) under observation in our centre over a one-year period (2003). Patients were evaluated about their renal function by means of serum creatinine dosage (mg/dL). The seriousness of AH was indirectly evaluated on the basis of the number of antihypertensive drugs taken daily.

Results: RI correlates with age (Pearson, 0.55/95% CI 0.32-0.71; p < 0.0001), and serum creatinine (Pearson, 0.58/ 95% CI 0.39-0.72; p < 0.0001). RI and serum creatinine do not differ in patient with or without ACE-I/ARB in their therapy (RI-Mann Whitney p = 0.517; creatinine-Mann Whitney, p = 0.0503). However, RI correlates with the number of antihypertensive drugs (Spearman rank correlation 0.59/95% CI 0.41-0.73; p < 0.001) and patients with three or more antihypertensive drugs in their therapy show higher RI than patients with one or no antihypertensive drugs (0.66 versus 0.8; independent samples t test, p < 0.0001).

Conclusions: in a small sample of kidney transplanted patients, RI is not influenced by ACE-I/ARB therapy, but by the amount of antihypertensive therapy.
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March 2005

[Two-chamber hemodiafiltration: comparison between exogenous reinfusion (PFD) and endogenous reinfusion (HFR)].

G Ital Nefrol 2004 Nov-Dec;21 Suppl 30:S111-6

U.O. di Nefrologia, Dialisi e Trapianto, ASL 2 Savonese, Presidio Ospedale San Paolo, Savona.

Purpose: This research aimed to compare two highly efficient dialysis techniques, paired filtration dialysis (PFD) and on-line hemodiafiltration with endogenous reinfusion (HFR) to evaluate the possible differences from a clinical, rehabilitative and managerial point of view.

Methods: The study was carried out on 14 patients (aged 40-65 yrs) six patients underwent PFD and eight patients underwent HFR. Patients on PFD came from low-flux hemodialysis (HD), while patients on HFR came either from PFD (n=5) or from low-flux HD (n=3). The research was based on the evaluation of patients inverted exclamation mark parameters (depurative and biochemical, level of clinical, medical and social rehabilitation) and of management parameters (technological aspects, cost analysis and medical-legal issues).

Results: HFR treatment improved plasmatic albumin values (> or =4.0 g/dL) and had a lower resistance to recombinant human erythropoietin (rHuEPO) therapy (by reducing the rHuEPO doses to reach the maintenance target values of hemoglobin (Hb) although both therapies resulted in equal depurative efficiency, and improved patient rehabilitation.

Conclusions: This preliminary research, which requires further confirmation, demonstrates that HFR seems to provide PFD with other positive benefits and offers the uremic patient a better life style.
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May 2005
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