Laryngeal injury in a coronavirus disease 2019 caregiver following voluntary cough-holding within an inappropriately sized personal protective equipment suit.

OBJECTIVE: To document laryngeal framework rupture following voluntary cough-holding as an airway complication of donning a personal protective equipment suit that was too small in size. METHODS: Clinical record and literature review, with proposition of plausible aerodynamics of the airway injury. RESULTS: Whilst carrying out his duty in the coronavirus disease ward, a resident attempted to stifle a paroxysm of cough when wearing a personal protective equipment suit that was too small with his neck flexed and restricted. There was a sudden release of pressure, intense pain and swelling in the neck with crepitus. Imaging revealed a non-displaced fracture in the lower end of the partially ossified right thyroid lamina, a cricothyroid membrane tear and subcutaneous emphysema. The symptoms resolved gradually on conservative management. CONCLUSION: This report underlines the importance of donning appropriately sized personal protective equipment and encouraging its proper use amongst coronavirus disease 2019 caregivers. Non-traumatic laryngeal injury, itself a rare event, has never been reported as a posture-related complication of wearing personal protective equipment.

Assessment of pain associated with bovine respiratory disease and its mitigation with flunixin meglumine in cattle with induced bacterial pneumonia.

Pleuritic chest pain from bacterial pneumonia is often reported in human medicine. However, studies investigating pain associated with bovine respiratory disease (BRD) are lacking. The objectives of this study were to assess if bacterial pneumonia elicits a pain response in calves with experimentally induced BRD and to determine the analgesic effects of transdermally administered flunixin. A total of 26 calves, 6-7 mo of age, with no history of BRD were enrolled into one of three treatment groups: 1) experimentally induced BRD + transdermal flunixin at 3.3 mg/kg twice, 24 h apart (BRD + FTD); 2) experimentally induced BRD + placebo (BRD + PLBO); and 3) sham induction + placebo (CNTL + PLBO). Calves induced with BRD were inoculated with Mannheimia haemolytica via bronchoalveolar lavage. Outcomes were collected from -48 to 192 h post-treatment and included serum cortisol, infrared thermography, mechanical nociceptive threshold, substance P, kinematic gait analysis, visual analog scale (VAS), clinical illness score, computerized lung score, average activity and rumination level, prostaglandin E2 metabolite, plasma serum amyloid A, and rectal temperature. Outcomes were evaluated using either a generalized logistic mixed model for categorical variables or a generalized linear mixed model for continuous variables. Right front force differed by treatment (P = 0.01). The BRD + PLBO had lower mean force applied to the right front limb (85.5 kg) compared with BRD + FTD (96.5 kg; P < 0.01). Average VAS differed by a treatment by time interaction (P = 0.01). The VAS scores differed for BRD + PLBO at -48 (3.49 mm) compared with 168 and 192 h (13.49 and 13.64 mm, respectively) (P < 0.01). Activity for BRD + PLBO was higher at -48 h (27 min/h) compared with 48, 72, 120, and 168 h (≤ 22.24 min/h; P < 0.01). Activity differed by a treatment by time interaction (P = 0.01). Activity for BRD + FTD was higher at -48 and 0 h (28.2 and 28.2 min/h, respectively) compared to 48, 72, 96, and 168 h (≤23.7 min/h; P < 0.01). Results show a combination of reduced activity levels, decreased force on the right front limb, and increased VAS pain scores all support that bacterial pneumonia in cattle is painful. Differences in right front force indicate that flunixin transdermal may attenuate certain pain biomarkers in cattle with BRD. These findings suggest that BRD is painful and analgesic drugs may improve the humane aspects of care for cattle with BRD.

Target Classification in Synthetic Aperture Radar Images Using Quantized Wavelet Scattering Networks.

The need to classify targets and features in high-resolution imagery is of interest in applications such as detection of landmines in ground penetrating radar and tumors in medical ultrasound images. Convolutional neural networks (CNNs) trained using extensive datasets are being investigated recently. However, large CNNs and wavelet scattering networks (WSNs), which share similar properties, have extensive memory requirements and are not readily extendable to other datasets and architectures-and especially in the context of adaptive and online learning. In this paper, we quantitatively study several quantization schemes on WSNs designed for target classification using X-band synthetic aperture radar (SAR) data and investigate their robustness to low signal-to-noise ratio (SNR) levels. A detailed study was conducted on the tradeoffs involved between the various quantization schemes and the means of maximizing classification performance for each case. Thus, the WSN-based quantization studies performed in this investigation provide a good benchmark and important guidance for the design of quantized neural networks architectures for target classification.

A non-invasive nanoparticle mediated delivery of triamcinolone acetonide ameliorates diabetic retinopathy in rats.

Diabetic retinopathy (DR) is a multifactorial manifestation associated with microvascular complications and is the fourth leading cause of visual impairment and blindness world-wide. Current day treatment of DR relies heavily on invasive techniques such as intravitreal injections of therapeutic agents. Unfortunately, intravitreal injections are associated with various complications such as intraocular bleeding, endophthalmitis, pain and discomfort resulting in poor patient compliance. To date, there has been no non-invasive drug delivery system reported for DR treatment. To address this, we developed a core-shell nanoparticle-based delivery system consisting of a hydrophobic polycaprolactone core and a hydrophilic Pluronic® F68 shell, loaded with triamcinolone acetonide and evaluated its efficacy in a DR rat model. After being administered as eye drops, the drug loaded nanoparticles significantly improved structural (retinal thickness and vascular health) and functional activity (rod and cone function) of retina as compared to DR controls that were treated with the drug alone or placebo nanoparticles. Furthermore, drug loaded nanoparticles reduced retinal inflammation as evidenced by a decrease in NF-κB, ICAM-1 and TNFα expression after 20 days of treatment. Similarly, a reduction in glial cell hyperplasia as evidenced by reduced GFAP expression, and a decrease in microvascular complications as evidenced by a decrease in VEGF secretion and microvascular tuft formation were observed in rat retinas after 40 days of treatment. The combined reduction in retinal inflammation and vascular abnormalities, both hallmarks of DR, demonstrates the potential of the nanoparticulate delivery system for use as a topical formulation for treating DR.

An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. γ-hydroxy-1,N2 -propanodeoxyguanosine (γ-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation. We examined the relationship of γ-OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in xeroderma pigmentosum group A knockout mice and diethylnitrosamine-injected mice, both prone to HCC development. γ-OHPdG levels in the livers of these animals were determined. The effects of antioxidant treatments on γ-OHPdG and hepatocarcinogenesis were examined. Using two independent sets of HCC specimens from patients, we examined the relationship between γ-OHPdG and survival or recurrence-free survival. γ-OHPdG levels in liver DNA showed an age-dependent increase and consistently correlated with HCC development in all three animal models. Theaphenon E treatment significantly decreased γ-OHPdG levels in the liver DNA of xeroderma pigmentosum group A knockout mice and remarkably reduced HCC incidence in these mice to 14% from 100% in the controls. It also effectively inhibited HCC development in the diethylnitrosamine-injected mice. Using clinical samples from two groups of patients, our study revealed that higher levels of γ-OHPdG are strongly associated with low survival (P < 0.0001) and low recurrence-free survival (P = 0.007). CONCLUSION: These results support γ-OHPdG as a mechanism-based, biologically relevant biomarker for predicting the risk of HCC and its recurrence. (Hepatology 2018;67:159-170).

Attenuation of diabetic retinopathy in rats by ellagic acid through inhibition of AGE formation.

Diabetic retinopathy (DR) is a major concern for blindness all over the world. Diabetic retinopathy is associated with thickening of basement membrane, retinal thinning, retinal detachment, and pericyte death. Advanced glycation end products (AGEs) mediate the progression of DR by stimulating the expression of RAGE and VEGF which subsequently damages the blood-retinal barrier. Employing a set of in vitro protein glycation systems, earlier we demonstrated antiglycating potential of ellagic acid (EA). In this study, we evaluated the efficacy of EA to prevent in vivo accumulation of AGE and to ameliorate retinal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed either with 0.2 or 2% EA in the diet for 12 weeks. Effect of EA on retinal function was assessed with electroretinogram (ERG). At the end of the experiment, rats were scarified and retina was collected. Histology was carried out with H&E staining and immunohistochemistry. Formation of AGE product (CML) and activation of RAGE was analyzed by immunoblotting and immunohistochemistry. Expression of GFAP, VEGF, Bax and HIF-1α was assessed by qRT-PCR and immunoblotting. Dietary supplementation of EA to diabetic rats resulted in: (1) inhibition of accumulation of CML and activation of RAGE in retina, (2) attenuation of expression of GFAP, VEGF, and HIF-1α in retina, (3) attenuation of cell death by reducing proapoptic mediator Bax and (4) amelioration of retinal thickness and function. In conclusion, EA attenuated the retinal abnormalities including angiogenesis, hypoxia and cell death by inhibiting AGE-RAGE mediated cellular events.

Citrus maxima (Pomelo) juice mediated eco-friendly synthesis of ZnO nanoparticles: Applications to photocatalytic, electrochemical sensor and antibacterial activities.

In the present work, Zinc oxide nanoparticles (ZnO Nps) have been successfully prepared through a simple, effective and low cost solution combustion method using Zn (NO3)2·6H2O as an oxidizer, chakkota (Common name=Pomelo) fruit juice as novel fuel. X-ray diffraction pattern indicates the hexagonal wurtzite structure with average crystallite size of ~22nm. ZnO Nps were characterized with the aid of different spectroscopic techniques such as Raman spectroscopy, Fourier Transform Infrared spectroscopy, Photoluminescence and UV-Visible spectroscopy. FTIR shows characteristic ZnO vibrational mode at 393cm-1. SEM images show that the particles are agglomerated. TEM image shows the size of the particles are about 10-20nm. Further, in order to establish practical applicability of the synthesized ZnO Nps, photocatalytic degradation of methylene blue (MB) dye as a model system was studied in presence of UV (665nm) light. In addition to this, the antibacterial activity was screen against 3 bacterial strains and electrochemical sensor performance towards the quantification of dopamine at nano molar concentrations was also explored.

Proton pump inhibitors in IPF: beyond mere suppression of gastric acidity.

Proton pump inhibitors (PPIs) are structurally composed of benzimidazole core; a pharmacologically common scaffold that makes up nearly one quarter of the hundred most selling drugs including anticancer, opioid, antihistaminic and antihelmintic drugs. In medicinal chemistry, benzimidazoles are coined as privileged scaffolds due to their ability to recognize and bind diverse biological targets. In this regard, PPIs have been linked to other extra-intestinal functions including direct modulation of airway epithelial, vascular endothelial and immune cells. PPIs have been reported to improve outcomes in idiopathic pulmonary fibrosis (IPF) including slowing the decline in measures of lung function, reducing episodes of acute exacerbations and prolonging transplant-free survival. Recently, the evidence-based guidelines for IPF treatment conditionally recommended the use of PPIs in IPF. However, no prospective clinical trial has been conducted to empirically evaluate the safety and efficacy of PPIs in IPF. Here, we discuss emerging anti-inflammatory and antifibrotic activity of PPIs in the context of IPF. We also discuss possible molecular mechanisms by which PPIs may unleash their beneficial effect in IPF.

Ellagic acid inhibits non-enzymatic glycation and prevents proteinuria in diabetic rats.

The formation of advanced glycation end products (AGEs) is a characteristic feature of diabetic tissues and accumulation of these products has been implicated in the pathogenesis of micro- and macrovascular complications of diabetes including diabetic nephropathy (DN). Compelling evidence suggests that AGEs mediate progressive alteration in the renal architecture and loss of renal function whereas inhibitors of AGEs prevent the progression of experimental DN. We have investigated the potential of ellagic acid (EA), a polyphenol present abundantly in fruits and vegetables, to prevent in vivo accumulation of AGE and to ameliorate renal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed with either 0.2% or 2% of EA in the diet for 12 weeks. Dietary supplementation of EA to diabetic rats prevented the glycation mediated RBC-IgG-cross-links and HbA1c accumulation. EA inhibited the accumulation of N-carboxymethyl lysine (CML), a predominant AGE in the diabetic kidney. Further, EA also prevented the AGE-mediated loss of expression of podocyte slit diaphragm proteins: nephrin and podocin. By inhibiting CML formation, EA improved renal function in rats as evidenced by urinary albumin and creatinine levels. In conclusion, EA inhibited AGE accumulation in the diabetic rat kidney and ameliorated AGE-mediated pathogenesis of DN.

Carboxymethyl lysine induces EMT in podocytes through transcription factor ZEB2: Implications for podocyte depletion and proteinuria in diabetes mellitus.

Advanced glycation end-products (AGEs) are implicated in the pathogenesis of diabetic nephropathy (DN). N-carboxymethyl-lysine (CML) is one of the predominant AGEs that accumulate in all renal compartments of diabetic patients. Nevertheless, the direct effect of CML on podocyte biology has not been explored. In this study, we demonstrate the induction of the transcription factor Zeb2 in podocytes upon exposure to CML through activation of NF-kB signaling cascade. Zeb2 orchestrates epithelial-mesenchymal transformation (EMT), during which cell-cell and cell-extracellular matrix interactions are feeble and enable epithelial cells to become invasive. CML treatment induced both NF-kB and Zeb2 promoter activity and suppressed E-cadherin promoter activity. Inhibition of NF-kB activity prevented CML dependent induction of Zeb2 and loss of E-cadherin. While the exposure of podocytes to CML results in increased podocyte permeability, shRNA-mediated knockdown of Zeb2 expression abrogated CML-mediated podocyte permeability. Further, in vivo findings of elevated CML levels concurrent with increased expression of ZEB2 in glomeruli and proteinuria in diabetic rats confirm that CML-mediated manifestations in the kidney under chronic diabetes conditions. These in vitro and in vivo results envisage the novel axis of NFkB-ZEB2 in podocytes playing a significant role in eliciting EMT and pathogenesis of DN.

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

Bronchiolitis obliterans syndrome (BOS) is a major complication of lung transplantation that is associated with poor survival. The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society convened a committee of international experts to describe and/or provide recommendations for 1) the definition of BOS, 2) the risk factors for developing BOS, 3) the diagnosis of BOS, and 4) the management and prevention of BOS. A pragmatic evidence synthesis was performed to identify all unique citations related to BOS published from 1980 through to March, 2013. The expert committee discussed the available research evidence upon which the updated definition of BOS, identified risk factors and recommendations are based. The committee followed the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to develop specific clinical recommendations. The term BOS should be used to describe a delayed allograft dysfunction with persistent decline in forced expiratory volume in 1 s that is not caused by other known and potentially reversible causes of post-transplant loss of lung function. The committee formulated specific recommendations about the use of systemic corticosteroids, cyclosporine, tacrolimus, azithromycin and about re-transplantation in patients with suspected and confirmed BOS. The diagnosis of BOS requires the careful exclusion of other post-transplant complications that can cause delayed lung allograft dysfunction, and several risk factors have been identified that have a significant association with the onset of BOS. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Adequately designed and executed randomised controlled trials that properly measure and report all patient-important outcomes are needed to identify optimal therapies for established BOS and effective strategies for its prevention.(AU)

Effect of cinnamon and its procyanidin-B2 enriched fraction on diabetic nephropathy in rats.

Non-enzymatic protein glycation and resultant accumulation of advanced glycation endproducts (AGE) are implicated in the pathogenesis of diabetic complications including diabetic nephropathy (DN). It is considered that antiglycating agents offer protection against AGE mediated pathologies including DN. Earlier we characterized procyanidin-B2 (PCB2) as the active component from cinnamon (Cinnamomum zeylanicum) that inhibits AGE formation in vitro. In this study, we have investigated the potential of PCB2-enriched fraction of cinnamon to prevent in vivo accumulation of AGE and to ameliorate renal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed with either 3% cinnamon or 0.002% PCB2-fraction in diet for 12weeks. Biochemical analysis of blood and urine was performed at the end of experiment. Evaluation of glomerular markers that serve as indicators of renal function was done by immunohistochemistry, immunoblotting and qRT-PCR. Supplementation of diabetic rats with cinnamon and PCB2-fraction prevented glycation mediated RBC-IgG cross-links and HbA1c accumulation in diabetes rats. Cinnamon and PCB2-fraction also inhibited the accumulation of N-carboxy methyl lysine (CML), a prominent AGE in diabetic kidney. Interestingly, cinnamon and its PCB2-fraction prevented the AGE mediated loss of expression of glomerular podocyte proteins; nephrin and podocin. Inhibition of AGE by cinnamon and PCB2-fraction ameliorated the diabetes mediated renal malfunction in rats as evidenced by reduced urinary albumin and creatinine. In conclusion, PCB2 from cinnamon inhibited AGE accumulation in diabetic rat kidney and ameliorated AGE mediated pathogenesis of DN.

Altered ubiquitin-proteasome system leads to neuronal cell death in a spontaneous obese rat model.

BACKGROUND: Obesity is associated with various progressive age-related diseases, including neurological disorders. However, underlying molecular basis for increased risk of neurodegeneration in obesity is unknown. A suitable animal model would immensely help in understanding the obesity-linked neurological problems. METHODS: A spontaneously developed obese rat (WNIN/Ob) which is highly vulnerable for a variety of degenerative diseases was isolated from the existing WNIN stock rats. Ultrastructure of neurons in the cerebral cortex of 12-month old obese rats was evaluated by transmission electron microscopy. qRT-PCR and immunoblotting of ubiquitin C-terminal hydrolases (UCHs), ubiquitin, proteasomal sub-units, markers of ER stress and apoptosis were performed in the cerebral cortex. Proteasome activity was assayed by fluorometric method. Immunohistochemistry was performed for mediators of apoptosis, which was further confirmed by TUNEL assay. These investigations were also carried in high-fat diet-induced obese rat model. RESULTS: Neurons in the cerebral cortex of 12-month obese rats showed swollen mitochondria, disrupted ER and degenerating axons, nucleus and finally neurons. Results showed altered UPS, existence of ER stress, up-regulation of apoptotic markers and apoptosis in the cerebral cortex of obese rats. It appears that UCHL-1 mediated apoptosis through stabilizing p53 might play a role in neuronal cell death in obese rat. Similar changes were observed in the brain of diet-induced obese WNIN rats. CONCLUSION: Altered UPS could be one of the underlying mechanisms for the neuronal cell death in obese conditions. GENERAL SIGNIFICANCE: This is the first report to highlight the role of altered UPS in neurodegeneration due to obesity.

Expression and induction of small heat shock proteins in rat heart under chronic hyperglycemic conditions.

The induction of small heat shock proteins (sHsp) is observed under various stress conditions to protect the cells and organisms from adverse events including diabetes. Diabetic cardiomyopathy is a common complication of diabetes. Therefore, in this study, we investigated the expression of sHsp under chronic hyperglycemic conditions in rat heart. Hyperglycemia was induced in WNIN rats by intraperitoneal injection of streptozotocin and maintained for a period of 12weeks. Expression of sHsp, phosphorylation and translocation of phosphoforms of Hsp27 and αB-crystallin (αBC) from cytosolic fraction to cytoskeletal fraction was analyzed. While the expression of MKBP, HspB3, αBC was found to be increased in diabetic heart, expression of Hsp20 was decreased. Chronic hyperglycemia further induced phosphorylation of αBC at S59, S45, Hsp27 at S82, p38MAPK and p44/42MAPK. However, pS59-αBC and pS82-Hsp27 were translocated from detergent-soluble to detergent-insoluble fraction under hyperglycemic conditions. Furthermore, the interaction of pS82-Hsp27 and pS59-αBC with desmin was increased under hyperglycemia. However, the interaction of αBC and pS59-αBC with Bax was impaired by chronic hyperglycemia. These results suggest up regulation of sHsp (MKBP, HspB3 and αBC), phosphorylation and translocation of Hsp27 and αBC to striated sarcomeres and impaired interaction of αBC and pS59-αBC with Bax under chronic hyperglycemia.

Covalent modification of glassy carbon spheres through ball milling under solvent free conditions: A novel electrochemical interface for mercury(II) quantification.

A simple and green chemistry protocol has been proposed based on the covalent anchoring of benzamide molecule on glassy carbon spheres through ball milling under solvent free condition. The modification proceeds through the formation of an amide bond between carboxylic group of glassy carbon spheres and the amino group of modifier molecule. The formation of covalent bond was ascertained using X-ray photoelectron spectroscopy. Scanning electron microscopy was used to study the surface morphology of milled glassy carbon spheres. The aqueous colloidal solution of modified glassy carbon spheres was used in the preparation of thin film electrodes and subsequently used as a novel electrochemical interface in the quantification of mercury at trace level using a differential pulse anodic stripping voltammetric technique. The modified electrode showed good sensitivity and selectivity towards mercury with a detection limit of 1nM with least interference from most of the ions. The analytical utility of the proposed electrode has been validated by determining the mercury levels in number of sample matrices.

Association of body burden of mercury with liver function test status in the U.S. population.

The majority of mercury (Hg) exposure in the US population is from consumption of fish contaminated with methylmercury (MeHg). Since inorganic Hg is the predominant form excreted in the feces and urine, hepatic biotransformation is a critical step in its normal clearance. This study was set to test the hypothesis that compromised liver function is associated with body burden of Hg as indirectly reflected by Hg sampled in blood and urine. From the National Health and Nutrition Examination Survey (NHANES, 2003-2008), 3769 adults aged 20 years and above were selected for analysis. Hepatic function was inferred from the three standard serum liver-related enzyme activities, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT). Multivariate regression models were used to examine the associations of interest. Although urinary Hg was significantly correlated with serum Hg, the blood-urinary Hg relationship was influenced by liver function, which is also a function of demographic and lifestyle factors (e.g., gender). Although the results were only marginally significant for examined enzymes (p=0.06-0.08), urinary Hg tended to be lower among subjects with elevated liver enzymes, as compared to those with normal enzyme measurements. Conversely, MeHg generally represents a higher fraction of the total circulating Hg among those with elevated liver enzyme levels, especially among participants with elevations in all three enzymes (p=0.01). In conclusion, this population-based study identified an association between liver function, serum Hg and urinary Hg. Urinalysis may not be the optimal approach to monitor Hg elimination toxicokinetics or Hg exposure, since the majority of Hg excretion is fecal and the fidelity of urinary excretion may depend on healthy liver function. Future prospective studies are warranted to expand these findings.

In vivo detection of a novel endogenous etheno-DNA adduct derived from arachidonic acid and the effects of antioxidants on its formation.

Previous studies showed that 7-(1',2'-dihydroxyheptyl)-substituted etheno DNA adducts are products of reactions with the epoxide of (E)-4-hydroxy-2-nonenal, an oxidation product of ω-6 polyunsaturated fatty acids (PUFAs). In this work, we report the detection of 7-(1',2'-dihydroxyheptyl)-1,N(6)-ethenodeoxyadenosine (DHHedA) in rodent and human tissues by two independent methods: a (32)P-postlabeling/HPLC method and an isotope dilution liquid chromatography-electrospray ionization-tandem mass spectrometry method, demonstrating for the first time that DHHedA is a background DNA lesion in vivo. We showed that DHHedA can be formed upon incubation of arachidonic acid with deoxyadenosine, supporting the notion that ω-6 PUFAs are the endogenous source of DHHedA formation. Because cyclic adducts are derived from the oxidation of PUFAs, we subsequently examined the effects of antioxidants, α-lipoic acid, Polyphenon E, and vitamin E, on the formation of DHHedA and γ-hydroxy-1,N(2)-propanodeoxyguanosine (γ-OHPdG), a widely studied acrolein-derived adduct arising from oxidized PUFAs, in the livers of Long Evans Cinnamon (LEC) rats. LEC rats are afflicted with elevated lipid peroxidation and prone to the development of hepatocellular carcinomas. The results showed that although the survival of LEC rats was increased significantly by α-lipoic acid, none of the antioxidants inhibited the formation of DHHedA, and only Polyphenon E decreased the formation of γ-OHPdG. In contrast, vitamin E caused a significant increase in the formation of both γ-OHPdG and DHHedA in the livers of LEC rats.

DAS181 treatment of severe parainfluenza type 3 pneumonia in a lung transplant recipient.

Parainfluenza virus (PIV) may cause life-threatening pneumonia in lung transplant patients and there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, to treat severe PIV type 3 pneumonia in a lung transplant patient. Treatment was well tolerated and associated with improvement in oxygenation and symptoms, along with rapid clearance of PIV. DAS181 should be systematically evaluated for treatment of PIV infection in transplant recipients.