Hyperbaric Oxygen Therapy for Cerebral Radiation Necrosis Secondary to Stereotactic Radiation: A Case Series

Introduction: Stereotactic radiosurgery (SRS) is an excellent option for the treatment of numerous central nervous system diseases. There exist several forms of SRS, including gamma-knife surgery (GKS) and cyber-knife surgery. The most significant complication of SRS is the delayed effects of therapeutic radiation, also known as radionecrosis. The current treatment options for radionecrosis have a significant side effect profile and posit challenges for medical management. More recently, hyperbaric oxygen therapy (HBO2) has emerged as an option for treatment with minimal side effects. Methods: We present a retrospective case series examining ten patients treated with HBO2 after receiving radiotherapy. Of these cases, six were treated with GKS, two were treated with cyber-knife surgery, and two with Intensity-modulated radiation therapy (IMRT). Results: In all ten cases, the patients reported significant improvement in clinical symptoms. Conclusions: These cases demonstrate the efficacy of HBO2 as a treatment for cerebral radionecrosis

Using DCFT for Multi-Target Detection in Distributed Radar Systems with Several Transmitters

In distributed radar systems, when several transmitters radiate simultaneously, the reflected signals need to be distinguished at the receivers to detect various targets. If the transmit signals are in different frequency bands, they require a large overall bandwidth. Instead, a set of pseudo-orthogonal waveforms derived from the Zadoff-Chu (ZC) sequences could be accommodated in the same band, enabling the efficient use of available bandwidth for better range resolution. In such a design, special care must be given to the 'near-far' problem, where a reflection could possibly become difficult to detect due to the presence of stronger reflections. In this work, a scheme to detect multiple targets in such distributed radar systems is proposed. It performs successive cancellations (SC) starting from the strong, detectable reflections in the domain of the Discrete Chirp-Fourier Transform (DCFT) after compensating for Doppler shifts, enabling the subsequent detections of weaker targets which are not trivially detectable. Numerical simulations corroborate the efficacy and usefulness of the proposed method in detecting weak target reflections

Sonochemistry: Applications in Biotechnology

Sonochemistry is a branch dealing with effects of chemical as well as sound wave as the name suggest. The sound waves are ultrasonic, i.e., high frequency waves (20 kHz can extent to 10 MHz and above) beyond the range of a human ear (20–20 kHz). Sonochemistry technology is incorporated into both mechanistic and synthetic studies. An important event called acoustic cavitation take place where microbubbles grow and under the influence of ultrasonic waves they collapse. Sonoluminescence is one of the outcomes of cavitation which leads to homogeneous sonochemistry. Sonochemistry has also entered one of the major developing field biotechnology from basic activation of enzyme to preparation of catalyst. It is also used for the fabrication of nanomaterial which comes under the liquid phase method. One disadvantage of nanomaterial preparation is the amount of time it consumes to show results. This can be eliminated when biotechnological research is conducted in conjunction with sonochemical application. Latest research results have proved that ultrasound irradiation is both time and cost-effective approach for any bio-processes like enhancement of emulsification and trans-esterification of fatty acids for bio-fuel products. Bio-process monitoring and dewatering of sludge have also been accelerated. This chapter contains introductory information on sonochemistry

Fibrinogen Replacement Therapy for Traumatic Coagulopathy : Does the Fibrinogen Source Matter?

Funding: This work was supported by an NIHR programme grant for applied research; PGfAR01590; “Traumatic coagulopathy and massive transfusion: improving outcomes and saving blood”.Peer reviewedPublisher PD

Atorvastatin and sildenafil decrease vascular TGF-β levels and MMP-2 activity and ameliorate arterial remodeling in a model of renovascular hypertension

AbstractImbalanced matrix metalloproteinase (MMP)-2 activity and transforming growth factor expression (TGF-β) are involved in vascular remodeling of hypertension. Atorvastatin and sildenafil exert antioxidant and pleiotropic effects that may result in cardiovascular protection. We hypothesized that atorvastatin and sildenafil alone or in association exert antiproliferative effects by down-regulating MMP-2 and TGF-β, thus reducing the vascular hypertrophy induced by two kidney, one clip (2K1C) hypertension.Sham and 2K1C rats were treated with oral atorvastatin 50mg/kg, sildenafil 45mg/kg, or both, daily for 8 weeks. Blood pressure was monitored weekly. Morphologic changes in the aortas were studied. TGF-β levels were determined by immunofluorescence. MMP-2 activity and expression were determined by in situ zymography, gel zymography, Western blotting, and immunofluorescence. The effects of both drugs on proliferative responses of aortic smooth muscle cells to PDGF and on on MMP-2 activity in vitro were determined. Atorvastatin, sildenafil, or both drugs exerted antiproliferative effects in vitro. All treatments attenuated 2K1C-induced hypertension and prevented the increases in the aortic cross-sectional area and media/lumen ratio in 2K1C rats. Aortas from 2K1C rats showed higher collagen deposition, TGF-β levels and MMP-2 activity and expression when compared with Sham-operated animals. Treatment with atorvastatin and/or sildenafil was associated with attenuation of 2K1C hypertension-induced increases in these pro-fibrotic factors. However, these drugs had no in vitro effects on hr-MMP-2 activity.Atorvastatin and sildenafil was associated with decreased vascular TGF-β levels and MMP-2 activity in renovascular hypertensive rats, thus ameliorating the vascular remodeling. These novel pleiotropic effects of both drugs may translate into protective effects in patients

Doped GeSe materials for selector applications

We report on the thermal and electrical performance of nitrogen (N) and carbon (C) doped GeSe thin films for selector applications. Doping of GeSe successfully improved its thermal stability to 450 degrees C. N doping led to a decrease in the off-state leakage and an increase in threshold voltage (V-th), while C doping led to an increase in leakage and reduced V-th. Hence, we show an effective method to tune the electrical parameters of GeSe selectors by using N and C as dopants

Mitochondria-Containing Extracellular Vesicles (EV) Reduce Mouse Brain Infarct Sizes and EV/HSP27 Protect Ischemic Brain Endothelial Cultures

Ischemic stroke causes brain endothelial cell (BEC) death and damages tight junction integrity of the blood-brain barrier (BBB). We harnessed the innate mitochondrial load of BEC-derived extracellular vesicles (EVs) and utilized mixtures of EV/exogenous 27 kDa heat shock protein (HSP27) as a one-two punch strategy to increase BEC survival (via EV mitochondria) and preserve their tight junction integrity (via HSP27 effects). We demonstrated that the medium-to-large (m/lEV) but not small EVs (sEV) transferred their mitochondrial load, that subsequently colocalized with the mitochondrial network of the recipient primary human BECs. Recipient BECs treated with m/lEVs showed increased relative ATP levels and mitochondrial function. To determine if the m/lEV-meditated increase in recipient BEC ATP levels was associated with m/lEV mitochondria, we isolated m/lEVs from donor BECs pre-treated with oligomycin A (OGM, mitochondria electron transport complex V inhibitor), referred to as OGM-m/lEVs. BECs treated with naïve m/lEVs showed a significant increase in ATP levels compared to untreated OGD cells, OGM-m/lEVs treated BECs showed a loss of ATP levels suggesting that the m/lEV-mediated increase in ATP levels is likely a function of their innate mitochondrial load. In contrast, sEV-mediated ATP increases were not affected by inhibition of mitochondrial function in the donor BECs. Intravenously administered m/lEVs showed a reduction in brain infarct sizes compared to vehicle-injected mice in a mouse middle cerebral artery occlusion model of ischemic stroke. We formulated binary mixtures of human recombinant HSP27 protein with EVs: EV/HSP27 and ternary mixtures of HSP27 and EVs with a cationic polymer, poly (ethylene glycol)-b-poly (diethyltriamine): (PEG-DET/HSP27)/EV. (PEG-DET/HSP27)/EV and EV/HSP27 mixtures decreased the paracellular permeability of small and large molecular mass fluorescent tracers in oxygen glucose-deprived primary human BECs. This one-two punch approach to increase BEC metabolic function and tight junction integrity may be a promising strategy for BBB protection and prevention of long-term neurological dysfunction post-ischemic stroke

Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer

Nitrite (NO2−) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the mechanism of nitrite-mediated cytoprotection is unknown, NO is a mediator of the ischemic preconditioning cell-survival program. Analogous to the temporally distinct acute and delayed ischemic preconditioning cytoprotective phenotypes, we report that both acute and delayed (24 h before ischemia) exposure to physiological concentrations of nitrite, given both systemically or orally, potently limits cardiac and hepatic reperfusion injury. This cytoprotection is associated with increases in mitochondrial oxidative phosphorylation. Remarkably, isolated mitochondria subjected to 30 min of anoxia followed by reoxygenation were directly protected by nitrite administered both in vitro during anoxia or in vivo 24 h before mitochondrial isolation. Mechanistically, nitrite dose-dependently modifies and inhibits complex I by posttranslational S-nitrosation; this dampens electron transfer and effectively reduces reperfusion reactive oxygen species generation and ameliorates oxidative inactivation of complexes II–IV and aconitase, thus preventing mitochondrial permeability transition pore opening and cytochrome c release. These data suggest that nitrite dynamically modulates mitochondrial resilience to reperfusion injury and may represent an effector of the cell-survival program of ischemic preconditioning and the Mediterranean diet

Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase–dependent manner

Nitrite (NO2−), previously viewed as a physiologically inert metabolite and biomarker of the endogenous vasodilator NO, was recently identified as an important biological NO reservoir in vasculature and tissues, where it contributes to hypoxic signaling, vasodilation, and cytoprotection after ischemia–reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin, deoxymyoglobin, xanthine oxidase, mitochondrial complexes, or NO synthase (NOS). We show that nitrite treatment, in sharp contrast with the worsening effect of NOS inhibition, significantly attenuates hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction, and mortality in a mouse shock model induced by a lethal tumor necrosis factor challenge. Mechanistically, nitrite-dependent protection was not associated with inhibition of mitochondrial complex I activity, as previously demonstrated for ischemia–reperfusion, but was largely abolished in mice deficient for the soluble guanylate cyclase (sGC) α1 subunit, one of the principal intracellular NO receptors and signal transducers in the cardiovasculature. Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were required. In conclusion, we show that nitrite can protect against toxicity in shock via sGC-dependent signaling, which may include hypoxic vasodilation necessary to maintain microcirculation and organ function, and cardioprotection