The Antioxidant Mechanisms Underlying the Aged Garlic Extract- and S-Allylcysteine-Induced Protection

Aged garlic extract (AGE) is an odorless garlic preparation containing S-allylcysteine (SAC) as its most abundant compound. A large number of studies have demonstrated the antioxidant activity of AGE and SAC in both in vivo—in diverse experimental animal models associated to oxidative stress—and in vitro conditions—using several methods to scavenge reactive oxygen species or to induce oxidative damage. Derived from these experiments, the protective effects of AGE and SAC have been associated with the prevention or amelioration of oxidative stress. In this work, we reviewed different antioxidant mechanisms (scavenging of free radicals and prooxidant species, induction of antioxidant enzymes, activation of Nrf2 factor, inhibition of prooxidant enzymes, and chelating effects) involved in the protective actions of AGE and SAC, thereby emphasizing their potential use as therapeutic agents. In addition, we highlight the ability of SAC to activate Nrf2 factor—a master regulator of the cellular redox state. Here, we include original data showing the ability of SAC to activate Nrf2 factor in cerebral cortex. Therefore, we conclude that the therapeutic properties of these molecules comprise cellular and molecular mechanisms at different levels

Ovulation failure in a Colombian Paso fino Mare : A combined antihomotoxic homeopathic therapy and hormonal treatment. A case report

ABSTRACT: Ovulation failure is one of the most frequent causes of infertility in mares. In the present case we report a six-year-old Colombian Paso Fino maiden Mare that was attended for breeding purposes with a previous history of ovulation failure. At ultrasound (US) examination of the reproductive tract and ovaries the left ovary measured 15 x 13 cm and a pathologic 13 x 11 cm diameter anecoic structure was diagnosed. The right ovary was found of normal size, and the uterus was found flacid. An anti homotoxic theraphy with Ovarium compositum®, Damiana injeel®, Cerebrum compositum®, and Phosphor hommacord® for 1½ months and FK (neural) therapy (twice/15 days) were then established, the ovary size was reduced, and softening of the follicular wall and a slight uterine response were observed. After 1½ month, the left ovary had 13 x 11 cm diameter and showed a 9 x 8 cm follicle, whereas the right ovary was multifollicular. Serum progesterone, estradiol and testosterone levels were those characteristics of an anestrous mare. The mare was treated with hCG (3.000 UI, i.v./3 days) and 4 days later a corpus luteum was diagnosed by US in the left ovary and serum progesterone levels raised to 14.91 ng/dl. At day 7 after hCG treatment the mare was given PGF2α (9 μg/kg/for two days) intramuscular, estrous was evident 5 days later, and artificial insemination (AI) with fertile semen was practiced resulting in a viable pregnancy as evaluated by ultrasound at day 20; however, this pregnancy was lost at 40 days after AI. The mare returned to estrus 20 days later, she was then inseminated and the resulting pregnancy was confirmed at day 20th resulting in a successful gestation and foaling of a full term viable foal. This report suggests hormonal therapy and alternative medicine could be successfully combined for treatment of specific ovarian pathologies in mares.RESUMEN: La falla ovulatoria es una de las principales causas de infertilidad en yeguas cíclicas. En el presente caso, se describe el seguimiento de una yegua nulípara de paso fino colombiano de seis años que ingresó a consulta para ser sometida a reproducción. Al examen ecográfico se le halló el ovario izquierdo de 15 x 13 cm con una estructura patológica de aspecto anecóico y contenido líquido de 13 x 11 cm, el ovario derecho sin estructuras y el útero flácido. La yegua fue sometida a tratamiento con antihomotóxicos del tipo Ovarium compositum®, Damiana injeel®, Cerebrum compositum®, y Phosphor hommacord® durante 1½ mes, y terapia FK (terapia neural, dos en 15 días), lo cual disminuyó el tamaño del folículo y del ovario, indujo ablandamiento de la pared folicular y leve respuesta uterina. Un mes y medio después, el ovario izquierdo tenía 13 x 11 cm y un folículo de 9 x 8 cm, y el ovario derecho estaba multifolicular. Las concentraciones de progesterona, estradiol y testosterona eran características de anestro. La yegua fue tratada con eCG (3.000 UI/3 días, i.v.), cuatro días después la progesterona ascendió a 14.91 ng/ dl, el examen ecográfico reveló un cuerpo lúteo en el ovario izquierdo y a los siete días fue tratada con PGF2α (9 μg/kg/2 días) intramuscular. Cinco días después la yegua presentó estro, fue inseminada y tuvo una gestación que perdió a los 40 días; luego presentó un nuevo estro a los 20 días, fue inseminada, se le confirmó gestación a los 20 días y tuvo una gestación a término con un potro viable al momento del parto. Este caso sugiere la posibilidad de combinar terapia hormonal con medicina alternativa para el tratamiento de algunos tipos de anormalidades en el funcionamiento ovárico en las yeguas

Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

Reply to "comment on 'Free-Radical Formation by the Peroxidase-Like Catalytic Activity of MFe2O4 (M = Fe, Ni, and Mn) Nanoparticles'"

Recently we have reported a qualitative, quantitative and reproducible study of the generation of free radicals as a result of the surface catalytic activity of Fe3O4, Fe2O3, MnFe2O4 and NiFe2O4 nanoparticles as a function of the Fe2+/Fe3+ oxidation state under different pHs (4.8 and 7.4) and temperatures (25 ºC and 40 ºC) condition. These results were contrasted with those obtained from the in vitro experiments in BV2 cells incubated with dextran-coated magneticnanoparticles. Based on these results we affirm that our ferrite magnetic nanoparticles catalyze the formation of free radicals and the decomposition of H2O2 by a ?peroxidase-like? activity. In a comment on this article, Meunier and A. Robert question two points: First they assert that the measured free radicals are not produced by a peroxidase reaction. Also, based on a different normalization method from those reported in our work, they also discuss that the reaction is not catalytic. Here we reply the arguments of the authors about these two points.Fil: Moreno Maldonado, Ana Carolina. Instituto de Nanociencia de Aragón; ; EspañaFil: Winkler, Elin Lilian. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Raineri Andersen, Mariana. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Toro Cordova, Alfonso. Universidad de Zaragoza; EspañaFil: Rodriguez, Luis Miguel. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Troiani, Horacio Esteban. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mojica Pisciotti, Mary Luz. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vasquez Mansilla, Marcelo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Tobia, Dina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Nadal, Marcela. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Torres Molina, Teobaldo Enrique. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: de Biasi, Emilio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Ramos, Carlos Alberto. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Goya, Gerardo Fabian. Universidad de Zaragoza; EspañaFil: Zysler, Roberto Daniel. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Lima, Enio Junior. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; Argentin

SMAC is expressed de novo in a subset of cervical cancer tumors

BACKGROUND: Smac/Diablo is a recently identified protein that is released from mitochondria after apoptotic stimuli. It binds IAPs, allowing caspase activation and cell death. In view of its activity it might participate in carcinogenesis. In the present study, we analyzed Smac expression in a panel of cervical cancer patients. METHODS: We performed semi quantitative RT-PCR on 41 cervical tumor and 6 normal tissue samples. The study included 8 stage I cases; 16 stage II; 17 stage III; and a control group of 6 samples of normal cervical squamous epithelial tissue. RESULTS: Smac mRNA expression was below the detection limit in the normal cervical tissue samples. In contrast, 13 (31.7%) of the 41 cervical cancer biopsies showed detectable levels of this transcript. The samples expressing Smac were distributed equally among the stages (5 in stage I, 4 in stage II and 4 in stage III) with similar expression levels. We found no correlation between the presence of Smac mRNA and histology, menopause, WHO stage or disease status. CONCLUSIONS: Smac is expressed de novo in a subset of cervical cancer patients, reflecting a possible heterogeneity in the pathways leading to cervical cancer. There was no correlation with any clinical variable

Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program

Introduction: Sodium ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects, with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients. Methods: NaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care (SOC) to hospitalized COVID-19 patients until oxygen saturation levels of > 94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 4 and October 31, 2020, are summarized. Results were compared with a retrospective contemporaneous control (CC) group of hospitalized COVID-19 patients with SOC alone during the same time frame from a subset of participating hospitals from Córdoba and Buenos Aires. Results: The evolution of 383 patients treated with SOC + NaIHS [56 on mechanical ventilation (MV) at baseline] and 195 CC (21 on MV at baseline) are summarized. At baseline, NaIHS-treated patients had basal oxygen saturation of 90.7 ± 0.2% (74.3% were on supplemental oxygen at baseline) and a basal respiratory rate of 22.7 ± 0.3 breath/min. In the CC group, basal oxygen saturation was 92.6 ± 0.4% (52.1% were on oxygen supplementation at baseline) and respiratory rate was 19.3 ± 0.3 breath/min. Despite greater pulmonary compromise at baseline in the NaIHS-treated group, the length of treatment (LOT) was 9.1 ± 0.2 gs with an average length of stay (ALOS) of 11.5 ± 0.3 days, in comparison with an ALOS of 13.3 ± 0.9 days in the CC group. In patients on MV who received NaIHS, the ALOS was lower than in the CC group. In both NaIHS-treated groups, a rapid reversal of deterioration in oxygenation and NEWS2 scores was observed acutely after initiation of NaIHS therapy. No serious adverse events were considered related to ibuprofen therapy. Mortality was lower in both NaIHS groups compared with CC groups. Conclusions: Treatment of COVID-19 pneumonitis with inhalational nebulized NaIHS was associated with rapid improvement in hypoxia and vital signs, with no serious adverse events attributed to therapy. Nebulized NaIHS s worthy of further study in randomized, placebo-controlled trials (ClinicalTrials.gov: NCT04382768).Fil: Salva, Oscar. Clínica Independencia; ArgentinaFil: Doreski, Pablo A.. Fundación Respirar; ArgentinaFil: Giler, Celia S.. Clínica Independencia; ArgentinaFil: Quinodoz, Dario C.. Sanatorio de la Cañada; ArgentinaFil: Guzmán, Lucia G.. Sanatorio de la Cañada; ArgentinaFil: Muñoz, Sonia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Carrillo, Mariana Norma del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Porta, Daniela Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Ambasch, Germán. Sanatorio Privado Mayo; ArgentinaFil: Coscia, Esteban. Sanatorio Privado Mayo; ArgentinaFil: Tambini Diaz, Jorge L.. Sanatorio Privado Mayo; ArgentinaFil: Bueno, Germán D.. Sanatorio Privado Mayo; ArgentinaFil: Fandi, Jorge O.. Clínica Independencia; ArgentinaFil: Maldonado, Miriam A.. Sanatorio San Roque; ArgentinaFil: Peña Chiappero, Leandro E.. Sanatori San Roque; ArgentinaFil: Fournier, Fernando. Clínica Francesa; ArgentinaFil: Pérez, Hernán A.. Sanatorio Alive; Argentina. University of Maryland; Estados UnidosFil: Quiroga, Mauro A.. Instituto Modelo de Cardiología; ArgentinaFil: Sala Mercado, Javier Agustin. Instituto Modelo de Cardiología; ArgentinaFil: Martínez Picco, Carlos. Clínica del Sol; ArgentinaFil: Beltrán, Marcelo Alejandro. Hospital Dr. Alberto Duhau; ArgentinaFil: Castillo Argañarás, Luis Fernando. Hospital Dr. Alberto Duhau; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ríos, Nicolás Martínez. Quimica Luar Srl; ArgentinaFil: Kalayan, Galia I.. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentin

Review: Strategies for enteric methane mitigation in cattle fed tropical forages

Methane (CH4) is a greenhouse gas (GHG) produced and released by eructation to the atmosphere in large volumes by ruminants. Enteric CH4 contributes significantly to global GHG emissions arising from animal agriculture. It has been contended that tropical grasses produce higher emissions of enteric CH4 than temperate grasses, when they are fed to ruminants. A number of experiments have been performed in respiration chambers and head-boxes to assess the enteric CH4 mitigation potential of foliage and pods of tropical plants, as well as nitrates (NO3−) and vegetable oils in practical rations for cattle. On the basis of individual determinations of enteric CH4 carried out in respiration chambers, the average CH4 yield for cattle fed low-quality tropical grasses (>70% ration DM) was 17.0 g CH4/kg DM intake. Results showed that when foliage and ground pods of tropical trees and shrubs were incorporated in cattle rations, methane yield (g CH4/kg DM intake) was decreased by 10% to 25%, depending on plant species and level of intake of the ration. Incorporation of nitrates and vegetable oils in the ration decreased enteric CH4 yield by ∼6% to ∼20%, respectively. Condensed tannins, saponins and starch contained in foliages, pods and seeds of tropical trees and shrubs, as well as nitrates and vegetable oils, can be fed to cattle to mitigate enteric CH4 emissions under smallholder conditions. Strategies for enteric CH4 mitigation in cattle grazing low-quality tropical forages can effectively increase productivity while decreasing enteric CH4 emissions in absolute terms and per unit of product (e.g. meat, milk), thus reducing the contribution of ruminants to GHG emissions and therefore to climate change

Inhibitors of apoptosis proteins in human cervical cancer

BACKGROUND: It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of c-IAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer. METHODS: We used semiquantitative RT-PCR assays to analyze 41 cancer and 6 normal tissues. The study included 8 stage I cases; 16 stage II; 17 stageIII; and a control group of 6 samples of normal cervical squamous epithelial tissue. RESULTS: c-IAP2 and XIAP mRNA levels were similar among the samples, cervical tumors had lower c-IAP1 mRNA levels. Unexpectedly, a clear positive association was found between low levels of XIAP and disease relapse. A log-rank test showed a significant inverse association (p = 0.02) between XIAP expression and tumor aggressiveness, as indicated by disease relapse rates. There were no statistically significant differences in the presence or expression levels of c-IAP1 and c-IAP2 among any of the clinical variables studied. Survivin and its isoforms were undetectable in normal cervical tissues, in contrast with the clear upregulation observed in cancer samples. We found no association between survivin expression and age, clinical stage, histology or menopausal state. Nevertheless, we found that adenocarcinoma tumors expressed higher levels of survivin 2B and DeltaEx3 (p = 0.001 and p = 0.04 respectively, by Kruskal-Wallis). A multivariate Cox's partial likelihood-based analysis showed that only FIGO stage was an independent predictor of outcome. CONCLUSION: There are no differences in the expression of c-IAP2 and XIAP between normal vs. cancer samples, but XIAP expression correlate in cervical cancer with relapse of this disease in the patients. Otherwise, c-IAP1 was downregulated in the cervical cancer samples. The expression of survivin was upregulated in the patients with cervical cancer. We have found that adenocarcinoma presented higher levels of survivin isoforms 2B and DeltaEx3

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio