1. From a single strain of Wistar rats two lines of normotensive rats (NR) and two lines of hypertensive rats (SHR) were developed by selective breeding.2. One line of normotensive rats and one of hypertensive rats were used as recipients and the remaining two were used as donors for cross-transplantation of kidneys from hypertensive to normotensive rats and vice versa. Transplantations between the two hypertensive lines and the two normotensive ones were carried out to provide animals for control studies.3. Normotensive recipients of kidneys from SHR developed hypertension whereas the recipients of kidneys from NR remained normotensive. The serum urea changes were equal in both groups.4. Transplantation of normotensive kidneys reduced the blood pressure of hypertensive recipients, but transplantation of hypertensive kidneys did not alter blood pressure. The serum urea concentrations were higher in the recipients of hypertensive kidneys. These results, obtained in 34-month-old rats, indicate that the kidneys of adult hypertensive rats are involved in the maintenance of hypertension. 5.To evaluate whether the kidneys from hypertensive rats may also initiate hypertension, young normotensive recipients were given kidneys taken from the NR or SHR strain while the latter were still normotensive. Transplantation of kidneys from these SHR donors resulted in si&cantly higher blood pressure values and serum urea concentrations than transplantation of kidneys from NR donors.

Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce(3+)/Ce(4+) redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields.

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Methimazole is an antithyroid drug that can induce loss of smell and taste in humans. It is also an olfactory toxicant in rodents. The aim of the present study was to examine involvement of glutathione in methimazole-induced damage of the olfactory mucosa (OM) of mice, and to study early onset of this damage using transmission electron microscopy (TEM). We found that an intraperitoneal dose of methimazole induced a dose-dependent decrease of nonprotein sulfhydryl groups (NP-SH; mainly glutathione) in the OM. Hepatic NP-SH was not decreased. One hour after administration (50 mg/kg), TEM demonstrated an extensive damage to acinar and intraepithelial excretory duct cells of Bowman's glands (BG) including dilatation of the endoplasmic reticulum and mitochondrial swelling. Furthermore, large vacuoles were noted in basal intraepithelial duct cells. After 2 hours there were ruptures of secretory granule membranes in BG and mitochondrial swelling and degeneration of sustentacular cells. The basal cells were less damaged. After four hours the neuroepithelium was disorganized although the columnar organization of neurons was largely intact. The acinar organization of the BG was frequently lost. The subsequent detachment of the neuroepithelium is suggested to be secondary to extensive damage of BG excretory ducts and sustentacular cells.

Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer’s disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions.

Guidelines, algorithms and recommendations have been issued in the attempt to ensure appropriateness of transfusion practice, but the results are less than satisfactory, mainly due to the difficulty to turn paper procedures into actual practice. In our hospital we have tried to overcome this difficulty through the implementation of a quality assurance programme which includes giving the privilege of nonurgent blood prescription to a limited number of physicians and a computerized prospective audit of blood requests. The latter is performed through verification of the compliance of blood requests, which are designed to include a patient's laboratory and clinical data, with hospital guidelines for the proper use of blood. In the 12 months since implementation of the computerized prospective audit the transfusion service has evaluated 7884 requests. Of these, 63.4% (n = 4998) were for red blood cells, 21.1% (n = 1664) for platelets and 15.5% (n = 1222) for fresh frozen plasma. The prospective audit showed that 96.8% and 98.1% of requests for red units and platelets were appropriate, respectively. Conversely, approximately 27% of plasma requests did not comply with guidelines, mainly because the evidence of coagulopathy was missing. However, inappropriateness of plasma requests for elective general surgery decreased from 39% at the onset of the programme to 14% in the last trimester considered. Moreover, the evaluation by retrospective audit of the proportion of patients transfused with both red blood cells and plasma in the perioperative period out of those transfused with red blood cells only, as an indicator of unwanted reconstitution of whole blood, showed that this proportion decreased from 47.6% (320/672) in the 12 months before implementation of computerized audit to 37.8% (244/646) in the following 12 months (difference = -9.8%, 95% confidence interval of the difference from -4.5% to -15.1%; P < 0.005 by chi 2 test). Our initial experience, together with the present system, shows that (1) the restriction of nonurgent blood prescription to a group of clinicians more educated in transfusion medicine than average clinicians practicing in a large multispecialty hospital is feasible; (2) prospective audit is a useful tool for assuring the quality of blood requesting.

Radiation therapy is one of the most effective methods of tumor eradication; however, in some forms of neuroblastoma, radiation can increase the risk of secondary neoplasms, due to the ability of irradiated cells to transmit pro-survival signals to non-irradiated cells through vesicle secretion. The aims of this study were to characterize the vesicles released by the human neuroblastoma cell line SH-SY5Y following X-ray radiations and their ability to increase invasiveness in non-irradiated SH-SY5Y cells. We first purified the extracellular vesicles released by the SH-SY5Y cells following X-rays, and then determined their total amount, dimensions, membrane protein composition, and cellular uptake. We also examined the effects of these extracellular vesicles on viability, migration, and DNA damage in recipient SH-SY5Y cells. We found that exposure to X-rays increased the release of extracellular vesicles and altered their protein composition. These vesicles were readily uptaken by non-irradiated cells, inducing an increase in viability, migration, and radio-resistance. The same results were obtained in an MYCN-amplified SK-N-BE cell line. Our study demonstrates that vesicles released from irradiated neuroblastoma cells stimulate proliferation and invasiveness that correlate with the epithelial to mesenchymal transition in non-irradiated cells. Moreover, our results suggest that, at least in neuroblastomas, targeting the extracellular vesicles may represent a novel therapeutic approach to counteract the side effects associated with radiotherapy.