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1.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526523

RESUMEN

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are used for treatment of type 2 diabetes, are associated with risk of urogenital infections. FDA issued a black box warning about multiple case reports of Fournier's gangrene (FG) observed in patients taking SGLT2 inhibitors. FG is a type of necrotising fasciitis that occurs in the anogenital area. We report a case of a 71-year-old woman with type 2 diabetes on dapagliflozin, presenting with foul-smelling discharge and a large abscess in the perianal area. Her risk factors for FG included her advanced age, obesity, diabetes and trauma to the site. During her stay, dapagliflozin was discontinued and she received procedural debridement, wound care and broad-spectrum intravenous antibiotics. Due to possible association between FG and SGLT2 inhibitors, patients presenting with signs and symptoms of FG who are taking SGLT2 inhibitors should be examined for infection in the urogenital area and treated promptly.


Asunto(s)
Absceso/inducido químicamente , Accidentes por Caídas , Compuestos de Bencidrilo/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gangrena de Fournier/inducido químicamente , Glucósidos/efectos adversos , Perineo/lesiones , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Absceso/terapia , Anciano , Antibacterianos/uso terapéutico , Desbridamiento , Diabetes Mellitus Tipo 2/complicaciones , Drenaje , Femenino , Gangrena de Fournier/terapia , Hospitales Rurales , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Linagliptina/uso terapéutico , Obesidad/complicaciones , Compuestos de Sulfonilurea/uso terapéutico
2.
Water Sci Technol ; 83(3): 567-579, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33600362

RESUMEN

In this study, hematite nanoparticles (HNPs) were used as the persulfate (PS) activator for the sonocatalytic degradation of bisphenol A (BPA). The physicochemical properties of the synthesized HNPs were investigated using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The effect of different operational parameters (pH, nanoparticle dosage, persulfate concentration, and ultrasonic power) on catalytic activity were evaluated. The BPA degradation rate was improved when ultrasonic (US) irradiation was used simultaneously with HNPs for activating PS. According to the results, 98.94% of BPA (10 mg/L) was degraded within 15 min of reaction time at 4 mM persulfate and 0.01 g/L HNPs under ultrasonic irradiation of 250 W. The degree of mineralization of BPA was measured using chemical oxygen demand (COD), and 36.98% was achieved under optimum conditions. Quenching tests were done using different scavenger compounds; these showed that both hydroxyl and sulfate radicals were reactive species in BPA degradation. According to the results of reusability tests, the degradation efficiency decreased to 86.34%, indicating that HNPs can be recycled several times. All of the anions tested, but mainly hydrogen phosphate, had an inhibitory effect on BPA degradation. The results showed that the US/HNPs/PS process is effective for the degradation of the organic pollutants.


Asunto(s)
Contaminantes Químicos del Agua , Compuestos de Bencidrilo , Fenoles , Contaminantes Químicos del Agua/análisis
3.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526518

RESUMEN

Immune checkpoint inhibitors (ICIs) are increasingly used to treat certain malignancies due to their higher efficacy compared with conventional chemotherapy. As familiarity with these agents increases, it is becoming apparent that a significant number of patients treated with ICIs experience adverse events. With time, more immune-related adverse events (IRAEs) are being recognised. It is important to be vigilant for IRAEs and recognise that a patient may have multiple IRAEs affecting multiple organ systems. Common cardiovascular adverse events associated with ICIs include myocarditis, arrhythmias and pericarditis. This case report identifies a patient presenting with takotsubo syndrome followed by ketoacidosis (associated with sodium-glucose transport protein 2 (SGLT2) inhibitor) in the setting of combination ipilimumab and nivolumab therapy for metastatic melanoma.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cetoacidosis Diabética/inducido químicamente , Melanoma/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Cardiomiopatía de Takotsubo/inducido químicamente , Anciano , Compuestos de Bencidrilo/efectos adversos , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/secundario , Angiografía Coronaria , Diabetes Mellitus Tipo 2/complicaciones , Cetoacidosis Diabética/complicaciones , Ecocardiografía , Glucósidos/efectos adversos , Humanos , Ipilimumab/efectos adversos , Imagen por Resonancia Magnética , Masculino , Melanoma/complicaciones , Melanoma/secundario , Nivolumab/efectos adversos , Cardiomiopatía de Takotsubo/complicaciones , Cardiomiopatía de Takotsubo/diagnóstico por imagen
14.
Mar Pollut Bull ; 163: 111931, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33418343

RESUMEN

Endocrine disrupting compounds (EDCs) in marine environments has become a major environmental concern. Nonetheless, the biological effects of EDCs on organisms in coastal environments remain poorly characterized. In this study, biomonitoring of EDCs in male fish Sebastiscus marmoratus was carried out in the Maowei Sea, China. The results showed that the concentration of 4-nonylphenol (4-NP) was below the detection limit, the concentrations of 4-tert-octylphenol (4-t-OP) and bisphenol A (BPA) in seawater were moderate compared with those in other global regions, and the possible sources are the municipal wastewater discharge. Nested ANOVA analyses suggest significant differences of the brain aromatase activities and plasma vitellogenin (VTG) expression between the port area and the oyster farming area. A new fish expert system (FES) was developed for evaluating the biological effects of EDCs on fish. Our findings show that the FES is a potential tool to evaluate the biological effects of marine pollutants.


Asunto(s)
Disruptores Endocrinos , Perciformes , Contaminantes Químicos del Agua , Animales , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/toxicidad , China , Disruptores Endocrinos/análisis , Disruptores Endocrinos/toxicidad , Monitoreo del Ambiente , Masculino , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
15.
Ecotoxicol Environ Saf ; 208: 111746, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396072

RESUMEN

Plasticizers are widespread environmental contaminants that have been described as obesogens in terrestrial vertebrates. However, its effects on fish lipids homeostasis are almost unknown. This work explores the use of PLHC-1 cells as an alternative model to assess the disruption of hepatic lipids by plastic additives and to gather information on the mode of action of these chemicals in fish. PLHC-1 lipid extracts were analyzed by flow injection coupled to high resolution mass spectrometry (FIA-ESI(+/-)-Orbitrap-Exactive) after 24 h exposure of the cells to the selected plasticizers: dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), bisphenol F (BPF), and chlorinated bisphenol A diglycidyl ether (BADGE·2HCl). The analysis of the culture medium and the intracellular concentration of the chemicals revealed the highest bioconcentration of BADGE·2HCl, DBP and DEHP, which was in agreement with the strongest alteration of the cells lipidome. BADGE·2HCl induced a significant depletion of triacylglycerides (TGs), while DEHP and DBP stimulated the accumulation of TGs. Exposure to BPF induced the generation of reactive oxygen species in PLHC-1 cells and a significant depletion of phosphatidylcholine (PC)- and phosphatidylethanolamine (PE)-plasmalogens, and TGs (cell depots of polyunsaturated fatty acids). Overall, this study evidences different modes of action of plastic additives in topminnow liver cells, describes differential lipidomic signatures, and highlights the higher lipotoxicity of BADGE·2HCl and BPF compared to BPA.


Asunto(s)
Plásticos/toxicidad , Pruebas de Toxicidad/métodos , Contaminantes Químicos del Agua/toxicidad , Animales , Compuestos de Bencidrilo , Dibutil Ftalato , Compuestos Epoxi , Fundulidae , Hepatocitos , Hígado/efectos de los fármacos , Modelos Biológicos , Fenoles , Ácidos Ftálicos , Plastificantes/toxicidad
16.
Environ Pollut ; 271: 116380, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33387779

RESUMEN

A vast amount of evidence indicates that bisphenol A (BPA) and phthalates are widely distributed in the environment since these compounds are mass-produced for the manufacture of plastics and plasticizers. These compounds belong to a large group of substances termed endocrine-disrupting chemicals (EDC). It is well known that humans and living organisms are unavoidably and unintentionally exposed to BPA and phthalates from food packaging materials and many other everyday products. BPA and phthalates exert their effect by interfering with hormone synthesis, bioavailability, and action, thereby altering cellular proliferation and differentiation, tissue development, and the regulation of several physiological processes. In fact, these EDC can alter fetal programming at an epigenetic level, which can be transgenerational transmitted and may be involved in the development of various chronic pathologies later in the adulthood, including metabolic, reproductive and degenerative diseases, and certain types of cancer. In this review, we describe the most recent proposed mechanisms of action of these EDC and offer a compelling selection of experimental, epidemiological and clinical studies, which show evidence of how exposure to these pollutants affects our health during development, and their association with a wide range of reproductive, metabolic and neurological diseases, as well as hormone-related cancers. We stress the importance of concern in the general population and the urgent need for the medical health care system to closely monitor EDC levels in the population due to unavoidable and involuntary exposure to these pollutants and their impact on human health.


Asunto(s)
Disruptores Endocrinos , Exposición a Riesgos Ambientales , Adulto , Compuestos de Bencidrilo/toxicidad , Política de Salud , Humanos , Fenoles/toxicidad
17.
Environ Pollut ; 271: 116304, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33401208

RESUMEN

Epidemiological studies have demonstrated that the general population's exposure to bisphenol A (BPA) substitutes is ubiquitous. Bisphenol F (BPF), one of the main BPA substitutes, is increasingly replacing BPA in plastics for food and beverage applications. Accumulating evidence suggests that BPA exposure is associated with nonalcoholic fatty liver disease (NAFLD)-like changes. However, the potential effects of BPF on lipid homeostasis remain poorly understood. In the present study, an epidemiological analysis with LC-MS-MS revealed that the BPF concentrations in the serum of NAFLD patients were significantly higher than those in a control group. Supporting this result, using Oil Red O, BODIPY 493/503, LipidTox Deep Red staining and gas chromatography-time-of-flight mass spectrometry (TOF-MS) assays, we found that BPF exposure induced NAFLD-like changes, with obvious lipid droplet deposition, triglyceride (TG) and fatty acids increase in mouse livers. Meanwhile, lipid droplet deposition and TG increase induced by BPF were also observed in HepG2 cells, accompanied by autophagic flux blockade, including autophagosome accumulation and the decreased degradation of SQSTM1/p62. Using adenoviruses dual-reporter plasmid RFP-GFP-LC3, RFP-GFP-PLIN2 transfection, AO staining, and EGFR degradation assays, we demonstrated that BPF treatment impaired lysosomal degradative capacity, since BPF treatment obviously impaired lysosomal acidification, manifested as decreased lysosomal hydrolase cathepsin L (CTSL) and mature cathepsin D (CTSD) in HepG2 and mouse liver issues. Additionally, v-ATPase D, a multi-subunit enzyme that mediates acidification of eukaryotic intracellular organelles, significantly decreased after BPF exposure in both the vitro and in vivo studies. This study ascertained a novel mechanism involving dysfunctional of lysosomal degradative capacity induced by BPF, which contributes to lipophagic disorders and causes lipid droplet deposition. This work provides evidence that lysosomes may be a target organelle where BPF exerts its potential toxicity; therefore, novel intervention strategies targeting lysosome are promising for BPF-induced NAFLD-like changes.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Compuestos de Bencidrilo/toxicidad , Humanos , Gotas Lipídicas , Lisosomas , Ratones , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Fenoles
18.
Chem Biol Interact ; 335: 109368, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33412153

RESUMEN

Dapagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, has featured marked anti-inflammatory effects in murine models of myocardial infarction, renal injury, and neuroinflammation. Yet, its potential impact on the pathogenesis of inflammatory bowel diseases (IBD) has not been previously investigated. The presented study aimed to explore the prospect of dapagliflozin to mitigate 2,4,6 trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model which recapitulates several features of the human IBD. The molecular mechanisms pertaining to the dynamic balance between autophagy/apoptosis and colon injury were delineated, particularly, AMPK/mTOR, HMGB1/RAGE/NF-κB and Nrf2/HO-1 pathways. The colon tissues were examined using immunoblotting, ELISA, and histopathology. Dapagliflozin (0.1, 1 and 5 mg/kg; p.o.) dose-dependently mitigated colitis severity as manifested by suppression of the disease activity scores, macroscopic damage scores, colon weight/length ratio, histopathologic perturbations, and inflammatory markers. More important, dapagliflozin enhanced colonic autophagy via upregulating Beclin 1 and downregulating p62 SQSTM1 protein expression. In this context, dapagliflozin activated the AMPK/mTOR pathway by increasing the p-AMPK/AMPK and lowering the p-mTOR/mTOR ratios, thereby, favoring autophagy. Moreover, dapagliflozin dampened the colonic apoptosis via lowering the caspase-3 activity, cleaved caspase-3 expression, and Bax/Bcl-2 ratio. Furthermore, dapagliflozin attenuated the HMGB1/RAGE/NF-κB pathway via lowering HMGB1, RAGE, and p-NF-κBp65 protein expression. Regarding oxidative stress, dapagliflozin lowered the oxidative stress markers and augmented the Nrf2/HO-1 pathway. Together, the present study reveals, for the first time, the ameliorative effect of dapagliflozin against experimental colitis via augmenting colonic autophagy and curbing apoptosis through activation of AMPK/mTOR and Nrf2/HO-1 pathways and suppression of HMGB1/RAGE/NF-κB cascade.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Compuestos de Bencidrilo/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Glucósidos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Colon/patología , Factor de Transcripción de la Proteína de Unión a GA/metabolismo , Proteína HMGB1 , Hemo Oxigenasa (Desciclizante)/metabolismo , Masculino , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Ácido Trinitrobencenosulfónico
19.
Food Chem ; 346: 128895, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33421902

RESUMEN

Bisphenols (BPs) are worldwide used organic compounds in plastics, belonging to the group of endocrine disrupting chemicals (EDCs) which exhibits endocrine disruption to beings. Migration of BPs from food contact materials like plastic containers, epoxy coatings in metal cans and thermal papers, would results in bioaccumulation of BPs in human beings, causing adverse health effects. Therefore, sensitive and selective determination of BPs in food is needed. Among different strategies have been explored for the detection of BPs, electrochemical sensors with relatively high sensitivity and fast response are promising. This paper is devoted to comprehensively review the developed electrochemical methods for BPs sensing in food, so that to find a direction for developing low cost, high accuracy and compatibility sensors toward the sensitive and selective detection of BPs. Different electrochemical technologies categorized by recognition agents, aptamers, enzymes, molecularly imprinted polymers and nanomaterials are discussed and summarized in their mechanisms, usages, merits and limitations. The challenges and further perspectives in the development of electrochemical sensors is also discussed.


Asunto(s)
Compuestos de Bencidrilo/análisis , Electroquímica/métodos , Análisis de los Alimentos/métodos , Fenoles/análisis , Disruptores Endocrinos/análisis , Contaminación de Alimentos/análisis , Humanos , Nanoestructuras/química
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(1): 93-99, 2021 Jan 30.
Artículo en Chino | MEDLINE | ID: mdl-33509759

RESUMEN

OBJECTIVE: To investigate the effect of environmental estrogen bisphenol A (BPA) exposure on apoptosis of mouse ovarian preantral follicular granulosa cells and ovarian development and explore the underlying mechanism. METHODS: Mouse ovarian preantral follicular granulosa cells were isolated from female ICR mice at postnatal day (PND) 10 and cultured in vitro. The cultured cells were treated with 0, 1, 10, 50, 100, 150, 200 and 500 µmol/L BPA, and the changes in cell proliferation, cell cycle, apoptosis and mitochondrial membrane potential were analyzed with CCK-8 method and flow cytometry. The protein expressions of Bcl-2, Bax, p53 and cyclin D1 in the treated cells were determined with Western blotting. Pregnant ICR mice were treated for a week with BPA at the concentration that produced significant effects on the preantral follicular granulosa cells, and the weight changes of the pregnant mice were recorded. The ovarian tissues of the offspring female mice were weighed at PND 10, 17, 21 and 42 followed by histological observation with HE staining and examination of Bcl-2 mRNA expression level with RT-qPCR. RESULTS: Compared with the control cells group, the isolated cells exposed to a low concentration of BPA (50 µmol/L) showed a significantly lowered apoptosis rate, increased mitochondrial membrane potential, and enhanced cellular proliferation (P < 0.05). Exposure to a higher BPA concentration at 200 µmol/L obviously enhanced cell apoptosis by reducing the mitochondrial membrane potential and repressed the cell proliferation (P < 0.05). BPA exposure at 50 µmol/L and 200 µmol/L produced opposite effects on the protein expressions of Bcl-2 (P < 0.01), Bax (P < 0.05) and p53 (P < 0.05) in mouse ovarian preantral follicular granulosa cells. BPA exposure at the doses of 10 and 35 mg/kg caused rapid weight increment of the pregnant mice and changes in ovarian index of the offspring female mice. In the offspring female mice, the changes in Bcl-2 mRNA expression in the ovarian tissue showed a similar pattern to that of ovarian index. Exposure of the pregnant mice to a high BPA concentration at 35 mg/kg resulted in accelerated follicular development into antral follicular stage in PND 21 offspring female mice. CONCLUSIONS: BPA can concentration-dependently regulate the function of ovarian preantral follicular granulosa cells in mice and potentially affects both the pregnant mice and the offspring female mice in light of early ovarian development.


Asunto(s)
Células de la Granulosa , Folículo Ovárico , Animales , Apoptosis , Compuestos de Bencidrilo , Femenino , Ratones , Ratones Endogámicos ICR , Fenoles , Embarazo
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