Abstract—Hafnium-silicate capacitors with 4.5-nm equivalent oxide thickness gate insulators were irradiated with 10-keV X-rays. The midgap and flatband voltage shifts in these devices increase linearly with dose and are significantly larger than the shifts seen in high quality, thermal SiO 2 gate oxides of similar electrical thickness. The standard trapping efficiency equation is adapted for calculating effective trapping efficiencies in alter- native dielectrics and used to compare the radiation response of hafnium silicate to SiO 2 from several manufacturers. The effects of common reliability screens such as “burn-in” and bias stress tests are also discussed. It is shown that baking these devices can degrade their capacitance-voltage characteristics, and large applied voltages inject excess charge into the dielectric, which can lead to a misinterpretation of the radiation results. However, the radiation responses of these devices, coupled with the demon- strated resistance of these films to heavy-ion induced gate rupture in previous studies, suggest that alternative dielectrics to SiO 2 potentially could be integrated into future electronics technologies for many low-power space applications.
Also sometimes classified as antibiotics, this group of compounds (doxorubicin, daunorubicin, epirubicin, mitoxantrone and others) forms the mainstay of many treatment regimens (Table 3). Their proposed mechanism of action involves topoisomerase II dependent DNA cleavage and subsequent intercalation with double stranded DNA. Although myelosuppression is universal with this group of compounds, it is their potential for cardiotoxicity that sets them apart. Acute effects include ECG changes (sinus tachycardia, nonspecific S-T wave changes, ectopic beats, low voltage QRS complexes), whereas chronic use causes dose-dependent cardiomyopathy. Retrospective analyses have suggested hypothetical totals for the following drugs, beyond which the incidence of cardiomyopathy steeply rises: 450mg/m 2 , 600mg/m 2 , and 100mg/m 2 cumulative total doses for doxorubicin, daunorubicin, and mitoxantrone, respectively. However, even in patients with normal resting cardiac function, prior anthracycline exposure may enhance the myocardial depressive effects of anaesthetics 10 . Known risk factors for doxorubicin - induced cardiomyopathy include prior/ current mediastinal radiotherapy, preexisting heart disease, concurrent cyclophosphamide or mitomycin use and the very young and very old patient. For daunorubicin the risk is increased in the elderly and the young. For mitoxantrone, mediastinal radiotherapy and prior doxorubicin use increase the risk of developing cardiomyopathy. Assessment for potential cardiotoxicity includes a history of cumulative dose, ECG and left ventricular ejection fraction estimation including wall motion abnormalities.
Administration of dietary antioxidants has been suggested to protect against the subsequent liver tissue damage. The present data to explore the hepatoprotective and antioxidant effect of anserine nitrate and /or zinc chloride against γ-irradiation induced hepatotoxicity. Healthy male albino rats were exposed to γ-irradiation from Co60 gamma cell 3500 at dose level (5.7 Gy) at a dose rate 2.67 rad/sec after 24 h and 14 days on the liver and to determine both prophylactic and therapeutic role of intraperitoneally administrated. Exposure to γ- irradiation induced a significant increase in levels of ALP, ALT and AST, while levels of glucose, total proteins, albumin, triglycerides, cholesterol, LDL-C, HDL-C, total, direct and indirect bilirubin and serum fractions were significantly decreased except for total lipids level which was almost not affected. Administration of anserine and/or zinc prior or after radiation exposure was found to offer protection against γ-irradiation induced hepatocellular damage and oxidative stress in rats, probably by exerting a protective effect against hepatocellular necrosis via its free radical scavenging and membrane stabilizing ability.
Abstract: The effects of Arabic gum (AG) against nephrotoxicity of mercury (Hg), an oxidative- stress inducing substance, in rats were investigated. A single dose of mercuric chloride (5 mg/kg intraperitoneal injection) induced renal toxicity, manifested biochemically by a significant increase in serum creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite production in kidney tissues. In addition, reduced glutathione, glutathione peroxidase, and catalase enzymes in renal tissues were significantly decreased. Pretreatment of rats with AG (7.5 g/kg/day per oral administration), starting 5 days before mercuric chloride injection and continuing through the experimental period, resulted in a complete reversal of Hg-inducedincrease in creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite to control values. Histopathologic examination of kidney tissues confirmed the biochemical data; pretreatment of AG prevented Hg-induced degenerative changes of kidney tissues. These results indicate that AG is an efficient cytoprotective agent against Hg-induced nephrotoxicity by a mechanism related at least in part to its ability to decrease oxidative and nitrosative stress and preserve the activity of antioxidant enzymes in kidney tissues.
Results: The results were compared with groups with only sodium arsenite exposure and groups which were exposed to only smokeless tobacco extract. Genotoxicity was evaluated by studying the incidence of micronucleated polychromatic erythrocytes from bone marrow. Both the tested doses of sodium arsenite induced statistically significant micronucleated polychromatic erythrocytes as compared to control group, however, sodium arsenite and smokeless tobacco extract could not increase the incidence of micronucleated polychromatic erythrocytes as compared to their individual counterparts when treated in combination in mice test system. Germ cell toxicity was evaluated by recording the sperm head abnormalities and total sperm count. Combined treatment of sodium arsenite and smokeless tobacco extract in lower doseinduced a significant increase in sperm head abnormality as compared to only sodium arsenite and smokeless tobacco extract. Liver, kidney and intestine tissues were analyzed for various oxidative stress evaluations such as lipid peroxidation (MDA), Glutathione (GSH) and superoxide dismutase (SOD) assay. Sodium arsenite in combination with smokeless tobacco extract show higher genotoxic and germ cell toxic effects as compared to control but not when compared to their individual counterparts.
This study was carried out to assess the protective effect and antioxidant activity of DPE against CsA induced nephrotoxicity. The results obtained revealed that SC injection of CsA in a dose of 15 mg/kg/d for 28 d resulted in the deterioration of renal function and the development of histopathological changes in the renal tissues. This was evidenced by a significant increase in serum levels of creatinine, blood urea nitrogen and uric acid compared with the Cont group. The obtained results were consistent with the most reported experimental procedures [2, 20, 21]. In addition, there was an elevation of serum albumin and ionic potassium with the reduction of serum total protein and ionic sodium levels as compared with the control rats. This effect confirmed the CsA nephrotoxicity effect. The obtained results were in agreement with the previously reported lesions of the CsA-induced nephrotoxicity .
Methods: This was a prospective observational population pharmacokinetic study in critically ill adult patients with presumed/confirmed invasive fungal infection. A single dose of 300 mg posaconazole was administered intravenously as an add-on to standard antifungal therapy, and serial plasma samples were collected over 48 h. Total and unbound posaconazole concentrations, measured by chromatographic method, were used to develop a population pharmacokinetic model and perform dosing simulations in R using Pmetrics. Results: From eight patients, 93 pairs of total and unbound concentrations were measured. A two-compartment linear model with capacity-limited plasma protein binding best described the concentration-time data. Albumin and body mass index (BMI) were included as covariates in the final model. Mean (SD) parameter estimates for the volume of the central compartment (V) and the elimination rate constant were 72 (43) L and 42.1 (23.7) h − 1 , respectively. Dosing simulations showed that high BMI was associated with a reduced probability of achieving target total and unbound posaconazole concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound posaconazole concentrations.
The relationship between stress and cytokine is regarded as important in re- cent years . IL-6 is produced by astrocytes and microglia in the brain  and is known as an inflammatory marker cytokine for schizophrenia, depression, anxiety disorder, and mood disorders caused by chronic stress  . Accord- ing to the recent findings, IL-6 regulates the activity of ERK (extracellular sig- nal-regulated kinases) which is an important second messenger regulating neu- ronal plasticity, and IL-6 indeed decreases hippocampal LTP and cortical synap- tic transmission . Therefore, the increase of inflammatory factor level in the prefrontal cortex may decrease the activity of this cortical area, which might re- sult in an increased emotional behavior controlled by the amygdala.
increase in the deposition of this mineral at the doses of 100 and 200 mg/kg. This could possibly be as a result of the high phosphorus content of our extract. In fact, dur- ing a bone healing process, calcium and phosphorus crystals derived from nutritional sources are deposited in bones in the form of hydroxyapatite  in the phase of bone mineralisation. This is in accordance with the results of calcium levels which have also increased in these groups. The increase mineralisation could equally be attributed to the presence of copper  in the ex- tract which enhances bone formation and skeletal mineralization . In the groups receiving the plant ex- tract at the dose of 400 mg/kg, there was a decrease in the bone mineral content to baseline values which could be due to the reduction in the activity of osteoblasts after fracture healing , leading to a decrease in mineralisation an hence in phosphorus deposition. This goes in line with the results of alkaline phosphatase ac- tivity and calcium content which equally reduced after administration of the plant extract at the dose of 400 mg/kg during 14 days.
Our data experimentally showed the chemosensitization of UA on hepatocellular carcinoma cisplatin-resistant HepG2/ DDP cells to low-dose cisplatin via Nrf2/ARE pathway and suggested that UA as a possible natural adjuvant sensitizer might have clinical significance with therapeutic capability on overcoming cisplatin-resistant hepatocellular carcinoma cells. However, different hepatocellular carcinoma cells, or even more other cancer cells, should be used for further study to see whether it is a universal phenomenon, or it occurs only in this cell line. Recently, many researches have suggested that the overcoming cisplatin resistance by using different adjuvant molecules and nanoparticle technology, 36,37
The most widely accepted hypothesis is that IAPP- induced cytotoxicity occurs via a membrane disruption mechanism. The experimental evidence suggested that the peptide Aβ, involved in Alzheimer’s disease, could form cation-selective channels in planar lipid bilayers . Simi- lar experiments showed that hIAPP could also form cation- selective channels and ultimately disrupt the membranes . These channels have been also observed for other amyloidogenic proteins suggesting that the toxicity of amyl- oid proteins seems to be linked to their shared potential to form pores in membrane [36, 37]. Many studies suggest hIAPP could induce membrane damage. But the exact mechanism of hIAPP-induced membrane disruption is far from clear. And numerous models have been described during recent years [38–41]. A report concluded that sol- uble oligomers from several types of amyloids, including hIAPP, specifically increase lipid bilayer conductance, while
constituted major chemical substances in the roots ex- tract. Evidence of the presence of flavonol/flavonoid/fla- vone or a related compound with polyhydroxy and/or phenolic groups is consistent with the significant antioxi- dant effect of the roots extract. Flavonoids or poly- phenolic substances exert antioxidant actions by scavenging free radicals, chelating metal ions or inhibit- ing enzyme systems that generate free radicals. Several studies demonstrated that flavonoids from various plants are reportedly capable of preventing the occurrence of gastric ulcer. This may take place through an increase in the amounts of neutral glycoproteins and in prostaglan- din concentrations, and inhibition of histamine secretion from mast cells by inhibition of histidine decarboxylase, thus reducing stimulation of H 2 receptors, or by secre-
Introduction: Acne arises during puberty, in part, due to elevated hormones and growth factors which stimulate de novo lipogenesis (DNL) in primary sebocytes to signi ﬁ cantly increase sebum production. Oral isotretinoin is an effective acne therapy, reducing sebum production through inducing apoptosis in sebocytes. However, isotretinoin is teratogenic and has additional unwanted side effects, including an initial acne ﬂ are-up, which limits its utility. The biguanide, metformin has been found to alleviate severe acne in women with polycystic ovary syndrome (PCOS) through normalization of their insulin and androgen hormone levels. Metformin ’ s broader effectiveness to improve acne in non-PCOS popula- tions lacks signi ﬁ cant clinical support. In an effort to determine whether biguanides directly affect sebogenesis, we investigated their ability to alter DNL in cell-based assays in vitro. Methods: De novo lipogenesis was measured in human primary sebocytes using [14C]- acetate labeling. Lipid species analysis was performed by extracting newly synthesized lipids and subjecting them to thin layer chromatography. Gene expression changes in sebocytes were identi ﬁ ed through qPCR analysis of isolated RNA. Metabolic parameters including oxygen consumption rate, lactate production and activation of adenosine monophosphate- dependent protein kinase (AMPK) were assessed in human primary sebocytes.
Notes: (A) Plasma glucose levels were determined 1 h after the administration of 80 mg/kg lca (solid line) or sitagliptin (5 mg/kg/day orally for 14 days; broken line) to the diabetic rats. Both groups were pretreated with the indicated dose of triamterene for 30 min. (B) Plasma glucose levels were determined 1 h after the administration of 50 mg/kg betulinic acid (solid line) or sitagliptin (5 mg/kg/day orally for 14 days; broken line) to the diabetic rats. Both groups were pretreated with the indicated dose of triamterene for 30 min. Values are expressed as the means ± se obtained from eight determinations per group. *P,0.05 and **P,0.01 compared with the vehicle-treated group. # P , 0.05 and ## P , 0.01 compared with the basal group without sitagliptin treatment.
In the present study, hosts seemed to increase defense, perhaps to a maximum, following exposure to a very low dose of parasite eggs, yet they did not increase defense at higher dose (Fig. 2). Therefore, even small exposures may be a sufficient cue that increases defense allocation in environments with a high risk of parasitism. One might expect a dose effect under the assumption that hosts would increase defense levels as more and more parasites were encountered, especially in sympatric host-parasite combinations that are more difficult to defend against. However, there was no effect of parasite dose or any higher order interactions involving dose, host source, or parasite source on hemocyte induction (Fig. 3, Table 3). There was a marginally significant parasite main effect for hemocyte induction (Table 3), meaning that some para- site populations might induce greater hemocyte responses than others. Potentially, coevolution may have increased counter-defenses in some trematode populations; thus, larger allocations to defense are required in the host when confronted with these parasites. Counter-defenses of par- asites are known to occur in many systems [22,23]. For example, interference of host hemocyte function has been shown in echinostomes (Trematoda) [24-26], and parasi- toids of Drosophila bury into the fat body in order to avoid circulating hemocytes .
integrity by neutrophils leads to kidney injury. Takasaki et al.  suggested that neutrophil cause kidney damage through the excessive release of oxygen radicals and pro- teases. In this study we observed a significant attenuation of MPO activity in the kidney tissue of quinacrine treated rats (Fig. 2). The exact mechanism by which quinacrine may reverse neutrophil mediated renal injury is not fully understood. Daniel et al.  reported a significant inhib- ition of neutrophil mediated superoxide generation and AA release by quinacrine. Earlier, anti-PLA2 antibodies have been shown to significantly suppress the neutrophil activity . Beside affecting innate and adaptive immun- ity neutrophils are well recognized as one of the major player during inflammatory damage to the tissues . Korrapati et al.  reported a significant increase in kid- ney NF-kB at 24 to 48 h after glycerol administration in rats. The available data clearly suggest that NF-kB and the major tumor suppressor P53 work in tandem in the pathogenesis of AKI [58, 59]. While NF-kB is a potent in- flammatory mediator and plays a major role in the synthe- sis of pro-inflammatory cytokines and chemokines , the anti-inflammatory effect of P53 seems to be universal . P53 has been shown to mitigate inflammation and exerts nephroprotective effect by several earlier investiga- tors [61, 62]. Quinacrine and its derivatives have been shown to suppress NF-kB and increased P53 protein by causing chromatin trapping of the FACT (facilitates chromatin transcription) complex [63, 64]. Moreover quinacrine has been shown to inhibit histamine methyl- transferase, a major enzyme responsible for catabolizing histamine, resulting in increased histamine level in kidney and other tissues . Histamine participates in regulation of wide variety of pathophysiological events including vasomotor actively and inflammatory responses. Hista- mine infusion directly in renal artery decreases renal vascular resistance and increased blood flow through its action on H1 and H2 receptors . Histamine through H1 receptors augment inflammatory responses ; whereas through H2 receptors it suppress inflammation by reducing inflammatory cytokines and chemokines [68, 69]. The ability of quinacrine to activate P53 and to inhibit NF-kB and histamine methyltrasferase may con- tribute to its nephroprotective activity [70, 71].
Doxorubicin (DOX) is an anthracycline antibiotic that is widely used as a chemotherapeutic agent. However, the administration of DOX is known to induce numerous cardiotoxic effects, including transient arrhythmias, nonspecific electrocardiographic abnormalities, pericarditis, and acute heart failure (Billingham et al, 1978 and Bristow et al, 1978). DOX can also cause congestive heart failure months or years after treatment. The mechanism of DOX-induced cardiac injury has been actively investigated, and several hypotheses have been suggested to explain the acute and chronic cardiotoxicity of DOX. Myocardial infarction (MI) is an acute condition of necrosis of the myocardium that occurs as a result of imbalance between coronary blood supply and myocardial demand ( De Bono and Boon, 1992). DOX-induced cardiotoxicity in rat was associated with increased lipid peroxide levels in the myocardium (Myers et al., 1977).
We present a case of a 62-year-old man who underwent total hip arthroplasty for treatment of pathologic femoral neck fracture associated with adefovir dipivoxil-induced osteomalacia. He had a 13-month history of bone pain involving his shoulders, hips, and knee. He received adefovir dipivoxil for treatment of lamivudine-resistant hepatitis B virus infection for 5 years before the occurrence of femoral neck fracture. Orthopedic surgeons should be aware of osteomalacia and pathological hip fracture caused by drug-induced renal dysfunction, which results in Fanconi ’ s syndrome.
To explore further the potential that crowd-out of existing financial aid ameliorated the potential positive benefits of the WSG, we next re-estimate treatment impacts according to whether the student attended a university where the WSG was often re-packaged to displace loans. Specifically, using the site variation in treatments impacts on total financial aid displayed in Table 7, Panel A, we distinguish between universities where students saw treatment impacts on total aid of less than $1,000 and those where treatment led to at least a $1,000 increase in total aid. This variation is largely attributable to (a) differences in how campuses packaged students’ financial aid awards after receiving the WSG, and (b) the amount of unmet need students had prior to receiving the grant (which is affected by both the institution’s cost of attendance and students’ willingness to accept loans). Table 6 shows the results, which suggest that all of the estimated positive treatment impacts on retention, credits, and grades accrued to students attending universities where the WSG resulted in at least a $1,000 increase in total financial aid by not crowding out loans. 31 This would seem to indicate that, at least in the short term, students benefit from the increased monetary resources associated with loans. It is too early to tell if students who saw their loans displaced by the program benefitted over the longer-term in other ways.
The actuator disk boundary condition is an internal boundary condition that imposes addition of flow field quantities to the flow through discontinuities that work according to the general momentum theory. (Glauert, 1963). Across the disk, mass flux is continuous, while there is a discontinuous jump in momentum and total energy flux. These discontinuous jumps are implicitly defined by specifying jumps in other variables. ZEN allows this to be done in two ways, that is, with a field model and a force model definition of boundary condition data. Because this report will only include simulations performed using boundary conditions defined for the force model because of the limited capability of unsteady ZEN, the field model will not be mentioned hereafter. The force model boundary condition distribution is defined in the following way.