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2.
Nature ; 606(7916): 873-877, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676486

RESUMO

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

4.
Nature ; 598(7880): 267-271, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34645999

RESUMO

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

5.
Environ Toxicol Pharmacol ; 80: 103464, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32750419

RESUMO

The identification of substances that prevent or minimize the detrimental effects of ionizing radiation is an essential undertaking. The aim of this paper was to evaluate and compare the radioprotective potential of chlorophyllin, protoporphyrin and bilirubin, with amifostine®, an US Food & Drug Administration approved radioprotector Using the somatic mutation and recombination assay in the Drosophila melanogaster wing, it was found that pretreatment (1-9 h) with any of the porphyrins or amifostine® alone, did not affect the larva-adult viability or the basal frequency of mutation. However, they were associated with significant reductions in frequency of somatic mutation and recombination compared with the gamma-irradiated (20 Gy) control as follows: bilirubin (69.3 %)> chlorophyllin (40.0 %)> protoporphyrin (39.0 %)> amifostine® (19.7 %). Bilirubin also caused a 16 % increase in larva-adult viability with 3 h of pretreatment respect to percentage induced in 20 Gy control group. Whilst amifostine® was associated with lower genetic damage after pre-treatment of 1 and 3 h, this did not attain significance. These findings suggest that the tested porphyrins may have some potential as radioprotectant agents.


Assuntos
Amifostina/farmacologia , Bilirrubina/farmacologia , Clorofilídeos/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/efeitos da radiação , Protoporfirinas/farmacologia , Protetores contra Radiação/farmacologia , Animais , Drosophila melanogaster/genética , Feminino , Masculino , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Recombinação Genética/efeitos dos fármacos , Asas de Animais/efeitos dos fármacos , Asas de Animais/efeitos da radiação
6.
Environ Toxicol Pharmacol ; 63: 16-20, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30121516

RESUMO

Ionizing radiation plays a key role in the adaptation of an individual organism to environmental pollution, at the same time, it has biological effects that depend on radiation intensity or dose rate (DR). Although the effect of DR has been studied in vitro, the phenomenon known as the inverse effect of DR, which indicates as it decreases that the induction of damage is greater, has not been widely studied in vivo. The present study is aimed to test 0.5 and 1 Gy in somatic cells of the wing of D. melanogaster, administered at 5.4 or 34.3 Gy/h and from 0.037 to 0.3 mM of CrO3 as conditioning treatment. No changes were found in larva-to-adult viability. A protective as well as a cross effect of pre-exposure to different DR and CrO3 concentrations against genetic damage induced by 20 Gy or 1 mM CrO3 was evident.


Assuntos
Compostos de Cromo/farmacologia , Drosophila melanogaster/genética , Asas de Animais/citologia , Animais , Meios de Cultivo Condicionados , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/efeitos da radiação , Feminino , Tolerância a Radiação , Radiação Ionizante , Asas de Animais/efeitos dos fármacos , Asas de Animais/efeitos da radiação
7.
J Toxicol Environ Health A ; 80(6): 365-373, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28644726

RESUMO

Casiopeinas® are a group of newly synthesized drugs designed to treat cancer. These copper (Cu) complexes exhibit cytostatic, cytotoxic, genotoxic, and antineoplastic activities through different mechanisms of action. To evaluate the influence of these compounds, some in vivo studies were performed using predominantly somatic cells. The aim of the present study was to examine the cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic as well as germ cells of Drosophila melanogaster. For cytotoxicity, the productivity and some morphometric parameters were measured and genotoxicity was assessed by means of the somatic mutation and recombination test assay in the wing. For this purpose, second-instar larvae of the Canton-S strain were treated with different concentrations of Cas III-Ea. The emerged adults were weighed, the area of the wings determined, and the number of trichomes of the region C' counted. The productivity of treated males was measured by a brood method to monitor the influence of Cas III-Ea on spermatozoa, meiotic stage cells, and spermatogonia. For genotoxicity, mwh + /+ flr3 larvae 48 hr age were chronically treated within the same concentration range. Results indicated that Cas III-Ea at all concentrations tested significantly increased the productivity per couple in Brood III (spermatids) while at 1 mM a marked elevation was noted in the three broods tested. In contrast, the weight and size of individuals as well as the size and number of cells in the wing were decreased significantly. Data suggest that Cas III-Ea is a weak genotoxic but selective mutagen. Failure to obtain a dose-related genotoxic response suggests that one of the preferred mechanisms of action of Cas III-Ea is to induce apoptosis.


Assuntos
Antineoplásicos/toxicidade , Complexos de Coordenação/toxicidade , Fenantrolinas/toxicidade , Animais , Drosophila melanogaster/efeitos dos fármacos , Feminino , Células Germinativas/efeitos dos fármacos , Masculino , Testes de Mutagenicidade , Asas de Animais/efeitos dos fármacos
8.
Environ Toxicol Pharmacol ; 48: 286-293, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27866098

RESUMO

The present study evaluates the superoxide dismutase (SOD) and catalase (CAT) activities in a wild strain of Drosophila melanogaster and the genotoxic potential induced by Cas II-gly (a new antineoplastic drug) using the somatic mutation and recombination test. Larvae 48h old were treated with Cas II-gly in a range of 0-1.5mM and aliquot were taken every 24h to have individuals treated for 24, 48, 72h and adulthood as well. A dose-dependent toxicity and a significant increase in SOD and CAT activities were found after a 24 and 48h treatment with 0.5-1.5mM concentrations. The comparison of the effect in enzymes with mutation indicated a positive correlation with increased genetic damage, after 24 and 48h of exposure for all concentrations tested. The addition of the genetic damage induced in each exposure time showed a significant effect, but only the small single spots had a concentration-related increase.


Assuntos
Antineoplásicos/toxicidade , Quelantes/toxicidade , Cobre/metabolismo , Mutagênicos/toxicidade , Compostos Organometálicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Catalase/metabolismo , Relação Dose-Resposta a Droga , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Feminino , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/genética , Masculino , Estresse Oxidativo/genética , Recombinação Genética/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Asas de Animais/efeitos dos fármacos
9.
Toxicol Rep ; 1: 894-899, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-28962301

RESUMO

Several epidemiological studies have reported the relation between chromium exposure (used in different industrial processes) and cancer risk. Evidence indicates that the hexavalent form is mutagenic and carcinogenic. Chemoprevention has emerged as a good strategy for reducing the risk from exposure to heavy metals. There is evidence that some tetrapyrrols such as protoporphyrin IX (PP-IX), a porphyrin without a metal center and which is a precursor of hemoglobin and cytochrome, acts as an antioxidant modulating the induction of antioxidant enzymes. The present study was performed to evaluate their antimutagenic potential of PP-IX against genetic damage induced by chromium trioxide (CrO3). The wing spot test was used. Groups of 48 h-old larvae were pretreated for 24 h with 0, 0.69, 6.9, or 69 mM of PP-IX, after which groups of larvae were fed 0.025-2.5 mM CrO3 solution in Drosophila instant medium. The results indicated that the lower PP-IX concentration (0.69 mM) significantly reduced the genetic damage induced by all CrO3 concentrations tested. In contrast, 6.9 and 69 mM only inhibited the damage induced by CrO3 2.5 mM. Absence of an inhibitor effect of PP-IX against 20 Gy gamma rays suggested that this porphyrin acted primarily by forming complexes with chromium at low doses, inactivating its genotoxic action rather than capturing or inactivating the reactive oxygen species generated by the chromium.

10.
Open AIDS J ; 5: 1-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21629502

RESUMO

In Northwestern Spain (NWS), the annual incidence of AIDS diagnoses increased from 1984 (when the first case was diagnosed) until 1996. However, since 1996, this incidence has reduced considerably, including a notable 40% reduction between 1997 and 1998. The Galician Register of AIDS supplies information on the evolution of AIDS pathology in NWS. This report compiles data on patients who were diagnosed with AIDS in NWS between 1984 and 2008. From 1981, when the first case of AIDS was described, until December 31, 2008, a total of 3,766 AIDS cases were registered in NWS. Of these, 2,085 cases (55.4%) resulted in death. Examining data from individual provinces revealed that the highest number of cases was in A Coruña (1,548 cases) followed by Pontevedra (1,485 cases).For almost half of the new cases of AIDS diagnosed between 2003 and 2008 (44%), less than six months passed between the diagnosis of infection and manifestations of the disease. Thus, the number of patients that do not receive early diagnosis of HIV infection has remained high.With regard to the transmission mechanism, 64% of the cases occurring during these years resulted from needle-sharing among injected drug users (IDUs). Unprotected heterosexual and homosexual practices were responsible for 20% and 17% of the cases, respectively.

11.
Mutat Res ; 722(1): 52-5, 2011 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-21406245

RESUMO

Sodium-copper chlorophyllin (SCC), a copper-porphyrin complex, has been shown to act as an inhibitor as well as a promoter of DNA-damage induction by a variety of mutagens in several test systems. In order to investigate the basis of this dual effect, experiments were carried out to compare the influence of pretreatment with intact SCC and that of its constituents, the metal-free protoporphyrin (PP-IX) and copper as CuCl(2). The wing-spot test was employed to monitor mutational events in somatic cells of Drosophila melanogaster. Heterozygous mwh+/+flr(3) larvae were treated for 24h with SCC, PP-IX, CuCl(2) or sucrose. Following this treatment, one group of larvae were immediately allowed to feed on instant medium containing 0.5mM N-nitroso-N-ethylurea (ENU) dissolved in phosphate buffer to reach pH 6. The remaining larvae received treatment with ENU with a delay of 1, 2 or 3days (DTD). Results revealed an (a) overall inhibitory effect for 0-DTD and 1-DTD after pretreatment with SCC, (b) only in 0-DTD after PP-IX, and (c) in all DTDs after treatment with CuCl(2). These results provide evidence that the copper ion plays a central role in the antimutagenic effect of SCC, and for a sustained period of time. Pretreatment with SCC and PP-IX produced a promoter effect at 2-DTD and 3-DTD. The results could be explained as an effect of the accumulation of metal-free porphyrin following the dissociation of the copper-porphyrin complex (SCC), the copper-ion reaching proteins to form complexes and participated in anabolic pathways.


Assuntos
Antimutagênicos/farmacologia , Clorofilídeos/toxicidade , Cobre/farmacologia , Etilnitrosoureia/toxicidade , Mutagênicos/farmacologia , Porfirinas/farmacologia , Animais , Clorofilídeos/química , Clorofilídeos/farmacologia , Drosophila/genética , Testes de Mutagenicidade , Relação Estrutura-Atividade
12.
Actas Dermosifiliogr ; 101(1): 54-8, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20109393

RESUMO

Hydroxychloroquine and chloroquine are antimalarials used as first-line treatment of cutaneous lupus. Quinacrine is not often employed by Spanish physicians due to a lack of information about its use and the fact that it is not marketed in Spain. It is effective in monotherapy or in combination therapy with other antimalarials. One of the advantages of quinacrine over chloroquine and hydroxychloroquine is that it does not appear to cause retinal toxicity. Quinacrine is used as second-line therapy in patients with pre-existing eye problems that contraindicate treatment with chloroquine or hydroxychloroquine (after evaluation of which drug has the better risk-benefit relationship), and in combination therapy with other antimalarials inpatients with resistance or only a partial response to chloroquine or hydroxychloroquine. We report 8 cases of patients with cutaneous lupus who received treatment with quinacrine in monotherapy or in combination with others antimalarials. Lesions resolved in 5 patients and improved in 3. Therapy had to be withdrawn in 1 patient due to an exacerbation of his psoriasis.


Assuntos
Lúpus Eritematoso Cutâneo/tratamento farmacológico , Quinacrina/uso terapêutico , Adulto , Anemia/induzido quimicamente , Cloroquina , Contraindicações , Feminino , Humanos , Hidroxicloroquina , Lúpus Eritematoso Discoide/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Paniculite de Lúpus Eritematoso/tratamento farmacológico , Psoríase/induzido quimicamente , Quinacrina/efeitos adversos , Quinacrina/química , Retina/efeitos dos fármacos , Relação Estrutura-Atividade , Adulto Jovem
15.
Mutat Res ; 679(1-2): 84-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19616118

RESUMO

It was first demonstrated in Salmonella that higher and lower concentrations of chlorophyllin (CHLN) may have effects in opposite directions, higher doses inhibiting and lower doses promoting the mutagenic activity of certain tobacco-related nitrosamines. Previous work of our group demonstrated that CHLN may have both a promoter and an inhibitory effect on mutagenesis in Drosophila. The present paper reviews the evidence obtained in our laboratory using gamma rays as the mutagenic agent, that higher and lower pretreatment concentrations of CHLN are associated with inhibitory and promoting effects, respectively, as in Salmonella. Employing the wing spot test, 48h larvae were pretreated with various concentrations of CHLN from 0 to 69 mM and then treated with 10 Gy gamma rays. With the highest concentration of CHLN, an approximate 54% reduction in mutagenesis was observed. At 35 mM a remnant of this inhibitory effect was found in that a significant decrease was limited to the twin spot category. Evidence of promotion was first seen at 4.3mM CHLN, an effect which persisted for the remaining five lower concentrations, the most pronounced evidence of promotion being found at the four lowest concentrations, 0.03-1.1 mM CHLN. It should be noted that no evidence of genotoxicity was found for CHLN alone, an observation consistent with the several reports in the literature. The results are taken as strong evidence that pretreatment with low concentrations of CHLN promotes DNA damage induced by gamma rays in somatic cells of Drosophila.


Assuntos
Clorofilídeos/farmacologia , Clorofilídeos/toxicidade , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Raios gama/efeitos adversos , Mutagênicos/toxicidade , Animais , Clorofilídeos/administração & dosagem , Relação Dose-Resposta a Droga , Drosophila/genética , Testes de Mutagenicidade , Protetores contra Radiação/farmacologia
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