Subacute oral toxicity investigation of selenium nanoparticles and selenite in rats

Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28?d with either: 0.05, 0.5, or 4?mg Se/kg body weight (bw)/day as 20?nm Se nanoparticles or 0.05 or 0.5?mg Se/kg bw/day as sodium selenite. Male rats were dosed 4?mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment. At necropsy, blood samples were taken for hematological and clinical chemistry analyses; organ weights were recorded. At the high-dose of Se nanoparticles, overt toxicity occurred and the female animals had to be euthanized prematurely, whereas the male animals were reduced in dose. At all doses of Se nanoparticles and at 0.5?mg Se/kg bw/day as selenite, a lower body weight gain as compared to vehicle occurred. Relative liver weight was increased for both Se formulations at 0.5?mg Se/kg bw/day. Creatinine clearance and urinary pH were affected in some Se dosed groups. There were no effects among dosed groups on brain neurotransmitters or on hematological parameters compared with controls. There were no histological changes in the livers of animals exposed to Se nanoparticles or to selenite. Based on effects on body weight and liver weight, selenium nanoparticles and ionic Se exerted similar toxicity. This suggests that a nanoparticle-specific toxicity of Se did not occur.     

Sexual victimization and completed suicide among danish female adults

Although sexual victimization has been associated with suicidal behaviors, its association with completed suicide has not been examined. We investigated this association among Danish women using longitudinal data and a conservative definition of victimization. This population-based case-control study included 476 suicide cases and 12,010 matched controls. Seven cases (1.5%) and 5 controls (0.04%) experienced sexual victimization that was reported to the police and resulted in a conviction. Sexual victimization was associated with a 14-fold increased rate of suicide, controlling for confounders and matching (95% CI: [3.4, 59]). Completed suicide is an important potential outcome of sexual victimization, warranting further examination.     

A Coupled CFD-DEM Study on the Effect of Basset Force Aimed at the Motion of a Single Bubble

The physical meaning of Basset force is first studied via polynomial approximation and the Fourier series representation method. After compiling the Basset force into the coupling interface with Visual C, a dynamic mathematical model is set up to describe the upward motion behavior of a single bubble by adopting the CFD-DEM method. Afterwards, the coupling interface with Basset force proposed in this study is verified experimentally and shows very good agreements. The initial velocity, releasing depth, bubble size, density ratio and viscosity ratio are studied qualitatively due to their great importance to Basset force. The ratio of Basset force to the sum of Basset force and drag force and to buoyancy, F→Ba/(F→D+F→Ba) and |F→Ba/F→B|, are employed to quantify the contribution of Basset force quantitatively. In addition, some instructive outlooks and recommendations on a further development of appropriate and justifiable use of Basset force are highlighted at last.     

Differential spectrofluorometry in the human vitreous: blood-retina barrier permeability to fluorescein and fluorescein glucuronide

A method is described for the separate quantitation of fluorescein and fluorescein glucuronide in the vitreous by differential spectrofluorometry. An ocular fluorometer was equppied with monochromatic laser excitation at two rapidly interchangeable wavelengths. The data analysis accounts for absorption of light in the cornea, lens, and extrinsic ocular fluorophores. Examination of seven patients with insulin-dependent diabetes and different degrees of diabetic retinopathy demonstrated that both fluorescein and fluorescein glucuronide enter the eye through the blood-retina barrier. The mean ratio between the permeabilities of fluorescein glucuronide and fluorescein was 0.9 (range, 0.3–1.9). Thus, differences in the molecular size and lipid solubility of the two substances appear to be of little or no importance for their inward penetration of the barrier. No association was found between the relative permeability and the degree of retinopathy.This study was supported by Danish Medical Research Council grant 12-8301 Offprint requests to: M. Larsen     

Amorphization and modified release of ibuprofen by post-synthetic and solvent-free loading into tailored silica aerogels

Promising active pharmaceutical ingredients (APIs) often exhibit poor aqueous solubility and thus a low bioavailability that substantially limits their pharmaceutical application. Hence, efficient formulations are required for an effective translation into highly efficient drug products. One strategy is the preservation of an amorphous state of the API within a carrier matrix, which leads to enhanced dissolution. In this work, mesoporous silica aerogels (SA) were utilized as a carrier matrix for the amorphization of the poorly water-soluble model drug ibuprofen. Loading of tailored SA was performed post-synthetically and solvent-free, either by co-milling or via the melting method. Thorough analyses of these processes demonstrated the influence of macrostructural changes during the drying and grinding process on the microstructural properties of the SA. Furthermore, interfacial SA-drug interaction properties were selectively tuned by attaching terminal hydrophilic amino- or hydrophobic methyl groups to the surface of the gel. We demonstrate that not only the chemical surface properties of the SA, but also formulation-related parameters, such as the carrier-to-drug ratio, as well as process-related parameters, such as the drug loading method, decisively influence the ibuprofen adsorption efficiency. In addition, the drug-loaded SA formulations exhibited a remarkable physical stability over a period of 6 months. Furthermore, the release behavior is shown to change considerably with different surface properties of the SA matrix. Hence, the reported results demonstrate that utilizing specifically processed and modified SA offers a compelling technique for enhancement of the bioavailability of poorly-water soluble APIs and a versatile adjustment of their release profile.     

Evolution of thrombolytic therapy in patients with HeartWare ventricular assist device thrombosis: a single-institutional experience

Open in a separate window OBJECTIVESPump thrombosis remains a major challenge in heart failure patients with left ventricular HeartWare assist device. Current International Society for Heart and Lung Transplantation recommendations favour surgical pump exchange over lysis because safety and efficacy of lysis has been controversially reported. This study summarizes our experience on our HeartWare thrombosis prevention strategy as well as thrombolysis through implementation of our institutional standardized HeartWare assist device protocol.METHODSOutcomes of all HeartWare thrombosis patients admitted between 2010 and 2020 were analysed. Thrombolysis therapy using tissue plasminogen activator was used as the first-line therapy in this study and thrombolysis therapy efficacy was defined as freedom from stroke, bleeding, recurrent HeartWare assist device thrombosis or surgical device exchange within 30 days after lysis application.RESULTSA total of 507 patients have been included in this study and 66 patients (13%) collectively developed a first HeartWare-thrombosis after a median of 12 months (8–22 months) after HeartWare implantation. Forty patients were treated with unstandardized lysis, of whom 7 patients had thrombolysis associated complications, such as incomplete thrombus resolution requiring surgical pump exchange in 4 patients, but also intracranial haemorrhage occurring in 3 patients. Three patients died in the non-protocol group. Eight device thrombosis patients were treated according to our protocol, showing no lysis-associated complication.CONCLUSIONSDespite current recommendations, preferring surgical HeartWare pump exchange in thrombosis, thrombolysis therapy for first HeartWare thrombosis can be safe and effective in a standardized protocol setting, including anticoagulation adjustment and intensified blood pressure control management.