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1.
Arch Toxicol ; 94(5): 1673-1686, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32253466

RESUMO

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are man-made chemicals that are used for the fabrication of many products with water- and dirt-repellent properties. The toxicological potential of both substances is currently under debate. In a recent Scientific Opinion, the European Food Safety Authority (EFSA) has identified increased serum total cholesterol levels in humans as one major critical effect being associated with exposure to PFOA or PFOS. In animal studies, both substances induced a decrease of serum cholesterol levels, and the underlying molecular mechanism(s) for these opposed effects are unclear so far. In the present study, we examined the impact of PFOA and PFOS on cholesterol homoeostasis in the human HepaRG cell line as a model for human hepatocytes. Cholesterol levels in HepaRG cells were not affected by PFOA or PFOS, but both substances strongly decreased synthesis of a number of bile acids. The expression of numerous genes whose products are involved in synthesis, metabolism and transport of cholesterol and bile acids was strongly affected by PFOA and PFOS at concentrations above 10 µM. Notably, both substances led to a strong decrease of CYP7A1, the key enzyme catalyzing the rate-limiting step in the synthesis of bile acids from cholesterol, both at the protein level and at the level of gene expression. Moreover, both substances led to a dilatation of bile canaliculi that are formed by differentiated HepaRG cells in vitro. Similar morphological changes are known to be induced by cholestatic agents in vivo. Thus, the strong impact of PFOA and PFOS on bile acid synthesis and bile canalicular morphology in our in vitro experiments may allow the notion that both substances have a cholestatic potential that is connected to the observed increased serum cholesterol levels in humans in epidemiological studies.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Ácidos e Sais Biliares/metabolismo , Caprilatos/toxicidade , Fluorocarbonos/toxicidade , Animais , Carcinoma Hepatocelular , Colesterol , Expressão Gênica , Hepatócitos , Homeostase , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Neoplasias Hepáticas
3.
Phys Rev Lett ; 111(12): 122501, 2013 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-24093252

RESUMO

Collinear laser spectroscopy was performed on the nuclear ground states of the neutron-deficient isotopes (206,205,204)Fr. A new technique was developed to suppress hyperfine pumping in collinear laser spectroscopy of atoms. This involved high-frequency intensity modulation of narrow-linewidth laser light using fast-switching electro-optical modulators. The nuclear ground-state spins of (206,205,204)Fr were determined to be 3, 9/2, and 3, respectively. Both the changes in mean-squared charge radii and nuclear magnetic dipole moments indicate a departure from single-particle estimates.

4.
Clin Case Rep ; 5(9): 1503-1509, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28878914

RESUMO

We report a novel KRT13 germ line variant that causes white sponge nevus (WSN) with mucosal dysplasia. Genital, vaginal, and cervical WSN were observed in four female patients, of whom two had premalignant cervical lesions at young age. Two of the 12 patients with oral WSN developed oral squamous cell carcinoma.

5.
J Craniomaxillofac Surg ; 42(7): 1412-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24864072

RESUMO

The purpose of this study is to: a) assess transport distraction to reconstruct cranial defects in radiated and non-radiated fields b) examine adipose grafting's effect on the bony regenerate and overlying wound, and c) elucidate sources of bone formation during transport distraction osteogenesis. Twenty-three male New Zealand white rabbits (3 months; 3.5 kg) were used, 10 non-irradiated and 13 irradiated (17 treatment, 6 control) with a one-time fraction of 35 Gy. A 16 × 16 mm defect was abutted by a 10 × 16 mm transport disc 5 weeks after irradiation, and 11 animals were fat grafted at the distraction site. Latency (1 day), distraction (1.5 mm/day), and consolidation (4 weeks) followed. Fluorochromes were injected subcutaneously and microCT, fluorescence, and histology assessed. In distracted animals without fat grafting, bone density measured 701.87 mgHA/ccm and 2271.95 mgHA/ccm in irradiated and non-irradiated animals. In distracted animals with fat grafting, bone density measured 703.23 mgHA/ccm and 2254.27 mgHA/ccm in irradiated and non-irradiated animals. Fluorescence revealed ossification emanating from the dura, periosteum, and transport segment with decreased formation in irradiated animals. Transport distraction is possible for cranial reconstruction in irradiated fields but short-term osseous fill is significantly diminished. Adipose grafting enhances wound healing in previously irradiated fields but does not enhance ossification.


Assuntos
Tecido Adiposo/transplante , Doenças Ósseas/cirurgia , Osteogênese por Distração/métodos , Procedimentos de Cirurgia Plástica/métodos , Crânio/cirurgia , Animais , Densidade Óssea/fisiologia , Densidade Óssea/efeitos da radiação , Doenças Ósseas/radioterapia , Regeneração Óssea/fisiologia , Regeneração Óssea/efeitos da radiação , Remodelação Óssea/fisiologia , Remodelação Óssea/efeitos da radiação , Dura-Máter/patologia , Dura-Máter/efeitos da radiação , Corantes Fluorescentes , Masculino , Osteogênese/fisiologia , Osteogênese/efeitos da radiação , Periósteo/patologia , Periósteo/efeitos da radiação , Coelhos , Dosagem Radioterapêutica , Distribuição Aleatória , Couro Cabeludo/patologia , Couro Cabeludo/efeitos da radiação , Crânio/efeitos da radiação , Retalhos Cirúrgicos/cirurgia , Cicatrização/fisiologia , Cicatrização/efeitos da radiação , Microtomografia por Raio-X/métodos
6.
Comp Med ; 64(3): 211-20, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24956213

RESUMO

Two aged female rhesus macaques (Macaca mulatta) presented with weight loss and intermittent inappetence. The signalment and constellation of clinical signs led clinicians to suspect the presence of intestinal adenocarcinoma. Because of each animal's advanced age and inconclusive radiographic findings, a noninvasive diagnostic tool was preferred over exploratory laparotomy to assist in determining a diagnosis. Consequently, 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-CT (FDG-PET-CT) was chosen to aid in confirming a suspicion of gastrointestinal adenocarcinoma in both animals. FDG is a glucose analogue labeled with fluorine-18 and is taken up by highly metabolically active cells, as observed in many cancers. Tomography revealed an annular constriction of the small intestine with focal FDG uptake in one animal, and an FDG avid transmural mass in the ascending colon of the second animal. Necropsy later confirmed both sites to be adenocarcinomas. This report supports the use of FDG-PET-CT as an adjunct to conventional radiography in the diagnosis of intestinal adenocarcinoma in nonhuman primates.


Assuntos
Adenocarcinoma/veterinária , Neoplasias Intestinais/veterinária , Macaca mulatta , Doenças dos Macacos/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Adenocarcinoma/diagnóstico , Animais , Feminino , Fluordesoxiglucose F18 , Neoplasias Intestinais/diagnóstico
7.
J Am Assoc Lab Anim Sci ; 52(1): 44-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23562032

RESUMO

We adapted a thermal analgesiometric device developed for cats for use in unrestrained rabbits. A probe composed of an electrical element and temperature sensor was held against shaved skin by using an elasticized band placed circumferentially around the thorax. An inflated bladder located between the probe and elastic maintained constant contact between probe and skin. The probe was heated until the rabbit displayed a behavioral reaction or the safety cutoff of 55 °C was reached. Threshold temperatures in unmedicated rabbits were stable over a 5-h period provided that tests were 15 min or more apart. Careful acclimation and testing resulted in no false-negative responses, and sham testing did not produce false-positive results. When compared with baseline values, thermal thresholds were significantly increased from 30 to 240 min, but not 300 min, after the administration of morphine at 3 mg/kg. Administration of equivalent volumes of saline via the same route had no effect on thermal threshold. This device may be suitable for investigating analgesic pharmacology in rabbits.


Assuntos
Analgésicos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Medição da Dor/veterinária , Coelhos , Animais , Feminino , Temperatura Alta , Morfina/farmacologia , Medição da Dor/instrumentação , Medição da Dor/métodos , Limiar Sensorial/efeitos dos fármacos , Limiar Sensorial/fisiologia , Sensação Térmica
8.
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