The impact of heme oxygenase-2 on pharmacological research: A bibliometric analysis and beyond

Heme oxygenase (HO-2) is an enzyme mainly involved in the physiologic turnover of heme and intracellular gas sensing, and it is very abundant in the brain, testes, kidneys and vessels. Since 1990, when HO-2 was discovered, the scientific community has underestimated the role of this protein in health and disease, as attested by the small amount of articles published and citations received. One of the reason that have contributed to the lack of interest in HO-2 was the difficulty in upregulating or inhibiting this enzyme. However, over the last 10 years, novel HO-2 agonists and antagonists have been synthesized, and the availability of these pharmacological tools should increase the appeal of HO-2 as drug target. In particular, these agonists and antagonists could help explain some controversial aspects, such as the neuroprotective versus neurotoxic roles of HO-2 in cerebrovascular diseases. Furthermore, the discovery of HO-2 genetic variants and their involvement in Parkinson’s disease, in particular in males, opens new avenues for pharmacogenetic studies in gender medicine

Discovery of an Accretion-rate Independent Absolute RMS Amplitude of Millihertz Quasi-periodic Oscillations in 4U 1636-53

We investigate the frequency and amplitude of the millihertz quasi-periodic oscillations (mHz QPOs) in the neutron-star low-mass X-ray binary 4U 1636?53 using Rossi X-ray Timing Explorer observations. We find that no mHz QPOs appear when the source is in the hard spectral state. We also find that there is no significant correlation between the frequency and the fractional RMS amplitude of the mHz QPOs. Notwithstanding, for the first time, we find that the absolute rms amplitude of the mHz QPOs is insensitive to the parameter S a , which measures the position of the source in the color?color diagram and is usually assumed to be an increasing function of mass accretion rate. This finding indicates that the transition from marginally stable burning to stable burning or unstable burning could happen very rapidly since, before the transition, the mHz QPOs do not gradually decay as the ratefurther changes.Fil: Lyu, Ming. Xiangtan University; ChinaFil: Méndez, Mariano. University Of Groningen. Kapteyn Astronomical Institute; AlemaniaFil: Altamirano, D.. University of Southampton; Reino UnidoFil: Zhang, Guobao. Chinese Academy Of Sciences; ChinaFil: Mancuso, Giulio Cesare. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; Argentin

Drifts of the marginally stable burning frequency in the X-ray binaries 4U 1608–52 and Aql X–1

We detect millihertz quasi-periodic oscillations (mHz QPOs) using the Rossi X-ray Time Explorer (RXTE) from the atoll neutron-star (NS) low-mass X-ray binaries 4U 1608-52 and Aql X-1. From the analysis of all RXTE observations of 4U 1608-52 and Aql X-1, we find mHz QPOs with a significance level >3σ in 49 and 47 observations, respectively. The QPO frequency is constrained between ∼4.2 and 13.4 mHz. These types of mHz QPOs have been interpreted as being the result of marginally stable nuclear burning of He on the NS surface. We also report the discovery of a downward frequency drift in three observations of 4U 1608-52, making it the third source that shows this behaviour. We only find strong evidence of frequency drift in one occasion in Aql X-1, probably because the observations were too short to measure a significant drift. Finally, the mHz QPOs are mainly detected when both sources are in the soft or intermediate states; the cases that show frequency drift only occur when the sources are in intermediate states. Our results are consistent with the phenomenology observed for the NS systems 4U 1636-53 and EXO 0748-676, suggesting that all four sources can reach the conditions for marginally stable burning of He on the NS surface. These conditions depend on the source state in the same manner in all four systems.Fil: Mancuso, Giulio Cesare. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Altamirano, D. University of Southampton; Reino UnidoFil: Méndez, M.. University Of Groningen; Países BajosFil: Lyu, M. Xiangtan University; ChinaFil: Combi, Jorge Ariel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; Argentin

XMM-Newton and NICER Measurement of the Rms Spectrum of the Millihertz Quasiperiodic Oscillations in the Neutron-star Low-mass X-Ray Binary 4U 1636–53

We used two XMM-Newton and six Neutron Star Interior Composition Explorer observations to investigate the fractional rms amplitude of the millihertz quasiperiodic oscillations (mHz QPOs) in the neutron-star low-mass X-ray binary 4U 1636?53. We studied, for the first time, the fractional rms amplitude of the mHz QPOs versus energy in 4U 1636?53 down to 0.2 keV. We find that, as the energy increases from ∼0.2 to ∼3 keV, the rms amplitude of the mHz QPOs increases, different from the decreasing trend that has been previously observed above 3 keV. This finding has not yet been predicted by any current theoretical model; however, it provides an important observational feature to speculate whether a newly discovered mHz oscillation originates from the marginally stable nuclear burning process on the neutron-star surface.Fil: Lyu, Ming. Xiangtan University; ChinaFil: Zhang, Guobao. Chinese Academy Of Sciences; ChinaFil: Méndez, Mariano. University Of Groningen, Kapteyn Astronomical Institute; AlemaniaFil: Altamirano, D.. University of Southampton; Reino UnidoFil: Mancuso, Giulio Cesare. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Xiang, Fu-Yuan. Xiangtan University; ChinaFil: Xiao, Huaping. Xiangtan University; Chin

Curcumin, Hormesis and the Nervous System

Curcumin is a polyphenol compound extracted from the rhizome of Curcuma longa Linn (family Zingiberaceae) commonly used as a spice to color and flavor food. Several preclinical studies have suggested beneficial roles for curcumin as an adjuvant therapy in free radical-based diseases, mainly neurodegenerative disorders. Indeed, curcumin belongs to the family of hormetins and the enhancement of the cell stress response, mainly the heme oxygenase-1 system, is actually considered the common denominator for this dual response. However, evidence-based medicine has clearly demonstrated the lack of any therapeutic effect of curcumin to contrast the onset or progression of neurodegeneration and related diseases. Finally, the curcumin safety profile imposes a careful analysis of the risk/benefit balance prior to proposing chronic supplementation with curcumin

Heme oxygenase-1 posttranslational modifications in the brain of subjects with Alzheimer disease and mild cognitive impairment. Free Radic.

a b s t r a c t Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Oxidative and nitrosative stress plays a principal role in the pathogenesis of AD. The induction of the heme oxygenase-1/biliverdin reductase-A (HO-1/BVR-A) system in the brain represents one of the earliest mechanisms activated by cells to counteract the noxious effects of increased reactive oxygen species and reactive nitrogen species. Although initially proposed as a neuroprotective system in AD brain, the HO-1/BVR-A pathophysiological features are under debate. We previously reported alterations in BVR activity along with decreased phosphorylation and increased oxidative/nitrosative posttranslational modifications in the brain of subjects with AD and those with mild cognitive impairment (MCI). Furthermore, other groups proposed the observed increase in HO-1 in AD brain as a possible neurotoxic mechanism. Here we provide new insights about HO-1 in the brain of subjects with AD and MCI, the latter condition being the transitional phase between normal aging and early AD. HO-1 protein levels were significantly increased in the hippocampus of AD subjects, whereas HO-2 protein levels were significantly decreased in both AD and MCI hippocampi. In addition, significant increases in Ser-residue phosphorylation together with increased oxidative posttranslational modifications were found in the hippocampus of AD subjects. Interestingly, despite the lack of oxidative stressinduced AD neuropathology in cerebellum, HO-1 demonstrated increased Ser-residue phosphorylation and oxidative posttranslational modifications in this brain area, suggesting HO-1 as a target of oxidative damage even in the cerebellum. The significance of these findings is profound and opens new avenues into the comprehension of the role of HO-1 in the pathogenesis of AD. & 2012 Elsevier Inc. All rights reserved. Introduction Increased oxidative and nitrosative stress represents one of the main mechanisms involved in the pathogenesis of neurodegenerative disorders such as Alzheimer disease (AD), which exhibits a large impairment of neuronal structure and molecular pathways due to oxidative stress-induced posttranslational modifications on both proteins and lipids AD is an age-related neurodegenerative disorder characterized histopathologically by the presence of senile plaques, neurofibrillary tangles (NFTs), and synapse loss in selected brain region

Serum 25-hydroxyvitamin D measurement: Comparative evaluation of three automated immunoassays

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PSR J0437-4715: The Argentine Institute of Radioastronomy 2019-2020 Observational Campaign

We present the first-year data set of high-cadence, long-duration observations of the bright millisecond pulsar J0437-4715 obtained in the Argentine Institute of Radioastronomy (IAR). Using two single-dish 30 m radio antennas, we gather more than 700 hr of good-quality data with timing precision better than 1 μs. We characterize the white and red timing noise in IAR´s observations, we quantify the effects of scintillation, and we perform single-pulsar searches of continuous gravitational waves, setting constraints in the nHz-μHz frequency range. We demonstrate IAR´s potential for performing pulsar monitoring in the 1.4 GHz radio band for long periods of time with a daily cadence. In particular, we conclude that the ongoing observational campaign of the millisecond pulsar J0437-4715 can contribute to increase the sensitivity of the existing pulsar-timing arrays.Fil: Sosa Fiscella, Sofía Valentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: del Palacio, Santiago. Universidad Nacional de La Plata; ArgentinaFil: Combi, Luciano. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Lousto, Carlos Oscar. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Combi, Jorge Ariel. Rochester Institute Of Technology; Estados UnidosFil: Gancio Gonzalez, Guillermo Matias. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: García, Federico. Universidad Nacional de La Plata; ArgentinaFil: Gutiérrez, Eduardo Mario. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Hauscarriaga, Fernando Pablo. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Kornecki, Paula. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Lopez Armengol, Federico Gaston. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Mancuso, Giulio Cesare. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Müller, Ana Laura. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Simaz Bunzel, Adolfo. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; Argentin

Estudio de alta precisión del púlsar J0437-4715 desde el Instituto Argentino de Radioastronomía

We used the two 30-m radio antennas at the Argentine Institute of Radioastronomy (IAR) to perform high-cadence observations of PSR J0437-4715, one of the nearest and brightest millisecond pulsars. Using this data set comprising +700 h of observations, we show that the timing precision currently achievable at IAR is ≈ 0.5 μs when accounting for different noise sources. We also identified and quantified the sources of timing error, analyzed the effects of scintillation due to the interstellar medium, and set constraints for single-pulsar searches of continuous gravitational waves. This study probes the potential of the IAR observatory to contribute with pulsar- timing arrays in the search for sources of long-period gravitational waves.Fil: Sosa Fiscella, Sofía Valentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Combi, Luciano. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: del Palacio, Santiago. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Lousto, Carlos Oscar. Rochester Institute Of Technology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Combi, Jorge Ariel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Gancio Gonzalez, Guillermo Matias. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: García, Federico. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Gutiérrez, Eduardo Mario. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Hauscarriaga, Fernando Pablo. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Kornecki, P.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Lopez Armengol, Federico Gaston. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Mancuso, Giulio Cesare. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Müller, Ana Laura. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Simaz Bunzel, Adolfo. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; Argentina62º Reunión Anual de la de la Asociación Argentina de AstronomíaRosarioArgentinaUniversidad Nacional de RosarioComplejo Astronómico Municipal “Galileo Galilei

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT