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1.
Aesthet Surg J ; 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402143

RESUMO

BACKGROUND: Breast implants are biomaterials eliciting a physiological and mandatory foreign body response. OBJECTIVES: We designed an animal study to investigate the impact of different implant surfaces on the formation of the perirprosthetic capsule, the inflammatory response and the cellular composition. METHODS: We implanted 1 scaled-down version of breast implants by different manufactures on 70 female Sprague Dawley rats. Animals were divided into five groups of 14 animals. Group A received a smooth implant (Ra≈0.5µm) according to the ISO 14607-2018 classification, Group B smooth implant (Ra≈3.2µm), Group C smooth implant (Ra≈5µm), Group D macrotextured implant (Ra≈62µm) and Group E macrotextured implant (Ra≈75µm). At 60 days, all animals received a magnetic resonance imaging (MRI) and 35 animals were sacrificed and their capsules sent for histology (capsule thickness, inflammatory infiltrate) and immunohistochemistry analysis (cellular characterization). The remaining animals repeated the MRI at 120 days and were sacrificed following the same protocol. RESULTS: MRI showed a thinner capsule in the smooth implants (Group A, B, C) at 60 days (p < 0.001) but not at 120 days (p = 0.039), confirmed with histology both at 60 days (p = 0.005) and 120 days (p < 0.001). Smooth implants (Group A, B, C) presented a mild inflammatory response at 60 days that was maintained at 120 days and a high M2-Macrophage concentration (anti-inflammatory). CONCLUSIONS: Our study confirms that smooth implants form a thinner capsule, inferior inflammatory infiltrate and a cellular composition that indicates a mild host inflammatory response. A new host inflammatory response classification is elaborated classifying breast implants into mild, moderate, and high.

2.
Biomolecules ; 12(2)2022 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-35204735

RESUMO

Serum levels of inflammatory cytokines are currently investigated as prognosis markers in myelofibrosis, the most severe Philadelphia-negative myeloproliferative neoplasm. We tested this hypothesis in the Gata1low model of myelofibrosis. Gata1low mice, and age-matched wild-type littermates, were analyzed before and after disease onset. We assessed cytokine serum levels by Luminex-bead-assay and ELISA, frequency and cytokine content of stromal cells by flow cytometry, and immunohistochemistry and bone marrow (BM) localization of GFP-tagged hematopoietic stem cells (HSC) by confocal microscopy. Differences in serum levels of 32 inflammatory-cytokines between prefibrotic and fibrotic Gata1low mice and their wild-type littermates were modest. However, BM from fibrotic Gata1low mice contained higher levels of lipocalin-2, CXCL1, and TGF-ß1 than wild-type BM. Although frequencies of endothelial cells, mesenchymal cells, osteoblasts, and megakaryocytes were higher than normal in Gata1low BM, the cells which expressed these cytokines the most were malignant megakaryocytes. This increased bioavailability of proinflammatory cytokines was associated with altered HSC localization: Gata1low HSC were localized in the femur diaphysis in areas surrounded by microvessels, neo-bones, and megakaryocytes, while wild-type HSC were localized in the femur epiphysis around adipocytes. In conclusion, bioavailability of inflammatory cytokines in BM, rather than blood levels, possibly by reshaping the HSC niche, correlates with myelofibrosis in Gata1low mice.


Assuntos
Citocinas , Fator de Transcrição GATA1 , Mielofibrose Primária , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Citocinas/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fator de Transcrição GATA1/metabolismo , Megacariócitos/metabolismo , Megacariócitos/patologia , Camundongos , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia
3.
Anim Biotechnol ; 33(6): 1142-1149, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33511904

RESUMO

Viruses belonging to the genus Norovirus (NoV) of the family Caliciviridae are the major cause of acute viral gastroenteritis worldwide. NoVs are classified into 10 genogroups (GI-GX), and those belonging to the genogroup GV are able to infect several species of rodents. To evaluate the circulation of MNV among mice housed in an Italian facility, sampling was performed over two separate periods, in 2011, and 3 years later in 2014. During the two samplings, 75 fecal samples were collected from healthy mice housed in the animal facility and subjected to RT-PCR for viral detection. After the analysis, 41/75 animals (54.6%) resulted positive for the presence of MNV in feces. Nucleotide sequencing revealed the presence of two MNV variants co-circulating in both 2011 and 2014. One MNV strain was isolated on RAW264.7 cell line, and subjected to full genome sequencing. Our study showed that the murine noroviruses are widespread in the investigated animal facility, despite guidelines for animal care and maintenance. Full genome sequence analysis of the MNV strain described in this study showed a correlation with other strains circulating in Europe. Understanding the molecular epidemiology of this virus should give insight into its natural history and evolution in mice.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Doenças dos Roedores , Camundongos , Animais , Norovirus/genética , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/etiologia , Gastroenterite/epidemiologia , Gastroenterite/veterinária , Gastroenterite/complicações , Fezes , Sequenciamento Completo do Genoma , Doenças dos Roedores/epidemiologia
4.
Reprod Toxicol ; 105: 17-24, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380069

RESUMO

Synthetic amorphous silica (SAS) consists of agglomerates and aggregates of primary particles in the nanorange (<100 nm) and it is the E551 authorized food additive. The potential risks for human health associated to dietary exposure to SAS are not completely assessed; in particular, data on male and female reproductive systems are lacking. A 90-day oral toxicity study with pyrogenic SAS nanomaterial NM-203 was carried out on the basis of the OECD test guideline 408 in the frame of the NANoREG project. Adult Sprague-Dawley rats of both sexes were orally treated for 90 days with 0, 2, 5, 10, 20 and 50 mg SAS/kg bw per day. Dose levels were selected to be as close as possible to the expected human exposure to food additive E551. The present paper provides specific information on potential effects on male and female reproductive systems, through the evaluation of serum biomarkers, sperm count, histopathological analysis of testis, epididymis, ovary and uterus and real-time PCR on uterus; potential genotoxic alterations were evaluated by comet assay on testis, sperm and ovary. NM-203 did not induce histophatological and genotoxic effects in male reproductive system. In female rats, ovary is not target of NM-203 and only tissue-specific effects on uterus were recorded up to 10 mg/kg bw per day. To our best knowledge, this is the first study providing data on male and female reproductive systems after long-term, repeated oral exposure at dose levels close to dietary human exposure, which identifies a limited concern only for female reproductive health.


Assuntos
Dióxido de Silício/toxicidade , Administração Oral , Animais , Ensaio Cometa , Estradiol/sangue , Feminino , Expressão Gênica/efeitos dos fármacos , Genitália/efeitos dos fármacos , Genitália/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Ratos Sprague-Dawley , Contagem de Espermatozoides , Testosterona/sangue , Testes de Toxicidade Subcrônica
5.
Toxicol Ind Health ; 37(6): 328-335, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33910434

RESUMO

Synthetic amorphous silica (SAS) nanomaterial - consisting of aggregates and agglomerates of primary silicon dioxide (SiO2) particles in the nanorange (<100 nm) - is commonly used as excipient in pharmaceuticals, in cosmetics and as food additive (E551). The available data suggest that SAS nanoparticles (NP) after intravenous (IV) exposure persist in liver and spleen; however, insufficient data exist to verify whether SAS may also induce adverse effects. The aim of the present study was to verify the potential long-term effects of SAS NP (NM-203) on spleen and liver as target organs following short-term exposure. Adult male and female Sprague-Dawley rats were treated by IV injection in the tail vein with a single (1-day) dose (SD) and repeated (5-day) doses (RD) of 20 mg/kg bw per day of SAS dispersed in sterile saline solution as vehicle. Histopathological examinations of target organs were performed after 90 days. Tissue biodistribution and full characterization of NM-203, primary particle size 13-45 nm, was performed within the framework of the Nanogenotox project. No mortality or general toxicity occurred; histopathological analysis showed splenomegaly in the RD group accompanied by inflammatory granulomas in both sexes. Granulomas were also present in liver parenchyma in the RD (both sexes) and SD groups (male only). The histopathological results indicated that SAS NP have the potential to persist and induce sex-specific chronic inflammatory lesions in spleen and liver upon short-term treatment. Overall, the data showed that the widespread use of silica in drugs might elicit chronic reactions in spleen and liver prompting to the need of further investigations on the safety of SAS NP.[Formula: see text].


Assuntos
Fígado/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Baço/efeitos dos fármacos , Administração Intravenosa , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Distribuição Tecidual
6.
Artigo em Inglês | MEDLINE | ID: mdl-33925988

RESUMO

BACKGROUND: The general population (including children) is exposed to chemical mixtures. Plasticizers such as Bisphenol A (BPA) and Phthalates (mainly Bis(2-ethylhexyl) phthalate-DEHP) are widespread contaminants classified as endocrine disrupters which share some toxicological profiles and coexist in food and environment. METHODS: To identify hazards of DEHP and BPA mixtures, the juvenile toxicity test-where rodents are in peripubertal phase of development, resembling childhood-was selected using exposure data from biomonitoring study in children. Biological activity and potential enhanced and/or reduced toxicological effects of mixtures due to common mechanisms were studied, considering endpoints of metabolic, endocrine and reproductive systems. The degree of synergy or antagonism was evaluated by synergy score calculation, using present data and results from the single compound individually administered. RESULTS: In metabolic system, synergic interaction predominates in female and additive in male rats; in the reproductive and endocrine systems, the co-exposure of BPA and DEHP showed interactions mainly of antagonism type. CONCLUSIONS: The present approach allows to evaluate, for all the endpoints considered, the type of interaction between contaminants relevant for human health. Although the mode of action and biological activities of the mixtures are not completely addressed, it can be of paramount usefulness to support a more reliable risk assessment.


Assuntos
Dietilexilftalato , Disruptores Endócrinos , Animais , Compostos Benzidrílicos/toxicidade , Criança , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Masculino , Fenóis/toxicidade , Ácidos Ftálicos , Plastificantes/toxicidade , Ratos
7.
Sci Adv ; 7(12)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33741595

RESUMO

Quantum key distribution-exchanging a random secret key relying on a quantum mechanical resource-is the core feature of secure quantum networks. Entanglement-based protocols offer additional layers of security and scale favorably with quantum repeaters, but the stringent requirements set on the photon source have made their use situational so far. Semiconductor-based quantum emitters are a promising solution in this scenario, ensuring on-demand generation of near-unity-fidelity entangled photons with record-low multiphoton emission, the latter feature countering some of the best eavesdropping attacks. Here, we use a coherently driven quantum dot to experimentally demonstrate a modified Ekert quantum key distribution protocol with two quantum channel approaches: both a 250-m-long single-mode fiber and in free space, connecting two buildings within the campus of Sapienza University in Rome. Our field study highlights that quantum-dot entangled photon sources are ready to go beyond laboratory experiments, thus opening the way to real-life quantum communication.

8.
Toxicology ; 449: 152653, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33309551

RESUMO

Bis(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in several items, non-covalently bound to plastics and easily released, since metabolites were found in human matrices. DEHP is an endocrine disrupter and children are particularly vulnerable and susceptible to DEHP effects due to higher exposure levels and developmental stage. A juvenile toxicity study was performed to identify DEHP hazard and mode of action in Sprague-Dawley rats of both sexes during peri-pubertal period - corresponding to childhood phase - from weaning, post-natal day (PND) 23, to full sexual maturity (PND60); the dose levels of 0, 9, 21 and 48 mg/kg bw/day were derived from LIFE PERSUADED biomonitoring study in children. DEHP was administered by gavage for 28 days (5 days/week); timing of preputial separation and vaginal opening was observed during treatment. Histopathological analysis was performed on: adrenals, spleen, liver, thyroid and reproductive organs. The following serum biomarkers were assessed: estradiol, testosterone, anti-Mullerian hormone, tetraiodothyronine, thyroid stimulating hormone, adiponectin and leptin. Gene expression on hypothalamic-pituitary area was focused on follicle stimulating, luteinizing, and thyroid stimulating hormones. The results showed that main targets of DEHP during juvenile period were liver and metabolic system in both sexes, while sex-specific effects were recorded in reproductive system (male rats) and in thyroid (female rats). DEHP exposure during peri-pubertal period at dose levels derived from biomonitoring study in children can induce sex-specific imbalances identifying the juvenile animal model as a sound tool to identify hazards for a reliable risk assessment targeted to children.


Assuntos
Monitoramento Biológico/métodos , Dietilexilftalato/toxicidade , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Administração Oral , Fatores Etários , Animais , Animais Recém-Nascidos , Criança , Dietilexilftalato/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Plastificantes/administração & dosagem , Plastificantes/metabolismo , Plastificantes/toxicidade , Ratos , Ratos Sprague-Dawley , Reprodução/fisiologia , Maturidade Sexual/fisiologia
9.
Food Chem Toxicol ; 137: 111168, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32007467

RESUMO

Food additive E551 consists of synthetic amorphous silica (SAS), comprising agglomerates and aggregates of primary particles in the nanorange (<100 nm), which potential nanospecific risks for humans associated to dietary exposure are not yet completely assessed. In NANoREG project, aim of the study was to identify potential hazards of pyrogenic SAS nanomaterial NM-203 by a 90-day oral toxicity study (OECD test guideline 408). Adult Sprague-Dawley rats of both sexes were orally treated with 0, 2, 5, 10, 20 and 50 mg SAS/kg bw per day; dose levels were selected to be as close as possible to E551 dietary exposure. Several endpoints were investigated, the whole integrative study is presented here along with the results of dispersion characterization, tissue distribution, general toxicity, blood/serum biomarkers, histopathological and immunotoxicity endpoints. No mortality, general toxicity and limited deposition in target tissues were observed. NM-203 affected liver and spleen in both sexes. Proposed NOAEL 5 mg/kg bw per day in male rats for enlarged sinusoids in liver. In female rats, TSH and creatinine levels were affected, proposed LOAEL 2 mg/kg bw per day. Overall, these data provide new insight for a comprehensive risk assessment of SAS exposure by the oral route.


Assuntos
Aditivos Alimentares/toxicidade , Nanoestruturas/toxicidade , Dióxido de Silício/toxicidade , Administração Oral , Animais , Biomarcadores/sangue , Feminino , Aditivos Alimentares/administração & dosagem , Fígado/patologia , Masculino , Nanoestruturas/administração & dosagem , Nível de Efeito Adverso não Observado , Ratos Sprague-Dawley , Medição de Risco , Silício/análise , Dióxido de Silício/administração & dosagem
10.
Nanotoxicology ; 8(6): 654-62, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23834344

RESUMO

The study explored possible reproductive and endocrine effects of short-term (5 days) oral exposure to anatase TiO2 nanoparticles (0, 1, 2 mg/kg body weight per day) in rat. Nanoparticles were characterised by scanning electron microscopy (SEM) and transmission electron microscopy, and their presence in spleen, a target organ for bioaccumulation, was investigated by single-particle inductively coupled plasma mass spectrometry and SEM/energy-dispersive X-ray. Analyses included serum hormone levels (testosterone, 17-ß-estradiol and triiodothyronine) and histopathology of thyroid, adrenals, ovary, uterus, testis and spleen. Increased total Ti tissue levels were found in spleen and ovaries. Sex-related histological alterations were observed at both dose levels in thyroid, adrenal medulla, adrenal cortex (females) and ovarian granulosa, without general toxicity. Altered thyroid function was indicated by reduced T3 (males). Testosterone levels increased in high-dose males and decreased in females. In the spleen of treated animals TiO2 aggregates and increased white pulp (high-dose females) were detected, even though Ti tissue levels remained low reflecting the low doses and the short exposure time. Our findings prompt to comprehensively assess endocrine and reproductive effects in the safety evaluation of nanomaterials.


Assuntos
Hormônios Esteroides Gonadais/sangue , Nanopartículas Metálicas/toxicidade , Baço/efeitos dos fármacos , Hormônios Tireóideos/sangue , Titânio/toxicidade , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Nanopartículas Metálicas/administração & dosagem , Ovário/química , Ovário/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Baço/química , Glândula Tireoide/química , Glândula Tireoide/efeitos dos fármacos , Distribuição Tecidual , Titânio/administração & dosagem , Aumento de Peso/efeitos dos fármacos
11.
Blood ; 114(10): 2107-20, 2009 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-19571316

RESUMO

Rigorously defined reconstitution assays developed in recent years have allowed recognition of the delicate relationship that exists between hematopoietic stem cells and their niches. This balance ensures that hematopoiesis occurs in the marrow under steady-state conditions. However, during development, recovery from hematopoietic stress and in myeloproliferative disorders, hematopoiesis occurs in extramedullary sites whose microenvironments are still poorly defined. The hypomorphic Gata1(low) mutation deletes the regulatory sequences of the gene necessary for its expression in hematopoietic cells generated in the marrow. By analyzing the mechanism that rescues hematopoiesis in mice carrying this mutation, we provide evidence that extramedullary microenvironments sustain maturation of stem cells that would be otherwise incapable of maturing in the marrow.


Assuntos
Medula Óssea/metabolismo , Elementos Facilitadores Genéticos , Fator de Transcrição GATA1/metabolismo , Regulação da Expressão Gênica , Hematopoese Extramedular , Células-Tronco Hematopoéticas/metabolismo , Animais , Fator de Transcrição GATA1/genética , Células-Tronco Hematopoéticas/citologia , Camundongos , Camundongos Mutantes , Mutação , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Estresse Fisiológico/genética
12.
Stem Cells ; 24(2): 337-48, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16144876

RESUMO

Two murine bipotent erythroid/megakaryocytic cells, the progenitor (MEP) and precursor (PEM) cells, recently have been identified on the basis of the phenotypes of linnegc-kitposSca-1neg CD16/CD32lowCD34low and TER119pos4A5pos or 2D5pos, respectively. However, the functional relationship between these two subpopulations and their placement in the hemopoietic hierarchy is incompletely understood. We compared the biological properties of these subpopulations in marrow and spleen of mice with and without acute or chronic erythroid stress. MEP cells, but not PEM cells, express c-kit, respond to stem cell factor in vitro, and form spleen colonies in vivo. PEM cells comprise up to 50%-70% of the cells in BFU-E-derived colonies but are not present among the progeny of purified MEP cells cultured under erythroid and megakaryocytic permissive conditions. PEM cells increase 10- to 20-fold under acute and chronic stress, whereas MEP cell increases (21%-84%) are observed only in acutely stressed animals. These data suggest that MEP and PEM cells represent distinct cell populations that may exist in an upstream-downstream differentiation relationship under conditions of stress. Whereas the dynamics of both populations are altered by stress induction, the differential response to acute and chronic stress suggests different regulatory mechanisms. A model describing the relationship between MEP, PEM, and common myeloid progenitor cells is presented.


Assuntos
Medula Óssea/metabolismo , Células Precursoras Eritroides/fisiologia , Eritropoese , Células-Tronco Hematopoéticas/fisiologia , Megacariócitos/citologia , Baço/metabolismo , Animais , Biomarcadores/análise , Diferenciação Celular , Células Precursoras Eritroides/metabolismo , Citometria de Fluxo , Fator de Transcrição GATA1/genética , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Fenil-Hidrazinas/farmacologia
13.
J Trace Elem Med Biol ; 18(2): 141-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15646260

RESUMO

We evaluated the presence of Ca, Na, K, Cu and Zn in the lenses and aqueous humour of rabbits treated with an Nd:YAG laser to induce opacity of the crystalline. The mean concentrations of the elements found in control lenses were: Ca: 15.8+/-5.2 mg/kg; Na: 1.2+/-0.6 g/kg; K: 10.3+/-3.3 g/kg; Cu: 0.19+/-0.06 mg/kg; Zn: 20.6+/-3.0 mg/kg. With the exception of K and Zn, the values found in the lenses of treated eyes (Ca: 135+/-24 mg/kg; Na: 4.3+/-1.5 g/kg; K: 10.1 +/- 3.2 g/kg; Cu: 0.47+/-0.17 mg/kg; Zn: 21.8+/-4.2 mg/kg) were significantly higher than in the controls. On the other hand, the concentrations found in the aqueous humour of treated eyes (Ca: 21.7+/-4.5 mg/l; Na: 0.66+/-0.21 g/l; K: 0.29+/-0.10 g/l; Cu: 0.035+/-0.009 mg/l; Zn: 0.079+/-0.01 mg/l) were significantly lower than those of the controls. The greatest difference was observed for Na (-68.6%) and Cu (-52.7%), followed by Ca and Zn (-35.0% and -35.2%, respectively). A positive correlation was found between Ca and Na in treated lenses (r2 = 0.9226, p < 0.0001) whereas inverse correlations were found for both Ca (r2 = 0.9788, p<0.0001) and Na (r2 = 0.9491, p<0.0001) between the concentrations found in the lenses and in the aqueous humour of treated eyes.


Assuntos
Humor Aquoso/química , Catarata/metabolismo , Cátions/análise , Cristalino/química , Animais , Cálcio/análise , Catarata/etiologia , Cobre/análise , Modelos Animais de Doenças , Lasers , Masculino , Potássio/análise , Coelhos , Sódio/análise , Espectrofotometria Atômica , Zinco/análise
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