Adenosine infusion increases plasma levels of VEGF in humans

BACKGROUND: Many in vitro studies have shown that adenosine (Ado) can induce vascular endothelial growth factor (VEGF) mRNA and protein expression and stimulate endothelial proliferation. In the present study, we seek to determine whether Ado can increase circulating levels of VEGF protein in the intact human. METHODS: Five outpatients 49.3 ± 6.7 years of age and weighing 88.2 ± 8.5 kg were selected. They were given a 6 min intravenous infusion of Ado (0.14 mg kg(-1 )min(-1)) in conjunction with sestamibi myocardial perfusion scans. Mean blood pressure (MBP, calculated from systolic and diastolic values) and heart rate (HR) were determined before Ado infusion and every 2 min for the next 10 min. Plasma VEGF concentrations (ELISA) were determined immediately before Ado infusion and 1 h, 2 h, and 8 h after the infusion. RESULTS: Plasma VEGF concentration averaged 20.3 ± 2.0 pg ml(-1 )prior to Ado infusion, and increased to 62.7 ± 18.1 pg ml(-1 )at 1 h post- infusion (p < 0.01). VEGF plasma concentration returned to basal levels 2 h after infusion (23.3 ± 3.4 pg ml(-1)). MBP averaged 116 ± 7 mmHg and heart rate averaged 70 ± 7 prior to Ado infusion. MBP decreased by a maximum of ~22% and HR increased by a maximum of ~17% during the infusion. CONCLUSION: We conclude from these preliminary findings that intravenous infusion of adenosine can increase plasma levels of VEGF in humans

How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide–copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue

Mercury retorting of calcine waste, contaminated soils and railroad ballast at the Idaho National Egineering Laboratory

The Idaho National Engineering Laboratory (INEL) has been involved in nuclear reactor research and development for over 40 years. One of the earliest major projects involved the development of a nuclear powered aircraft engine, a long-term venture which used mercury as a shielding medium. Over the course of several years, a significant amount of mercury was spilled along the railroad tracks where the test engines were transported and stored. In addition, experiments with volume reduction of waste through a calcine process employing mercury as a catalyst resulted in mercury contaminated calcine waste. Both the calcine and Test Area North wastes have been identified in Department of Energy Action Memorandums to be retorted, thereby separating the mercury from the various contaminated media. Lockheed Idaho Technologies Company awarded the Mercury Retort contract to ETAS Corporation and assigned Parsons Engineering Science, Inc. to manage the treatment field activities. The mercury retort process entails a mobile unit which consists of four trailer-mounted subsystems requiring electricity, propane, and a water supply. This mobile system demonstrates an effective strategy for retorting waste and generating minimal secondary waste

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants

Objective This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants. Study Design In this retrospective database study, we included all ELBW infants who were 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed. Results A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91-2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02-1.76). Conclusions Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP.National Center for Advancing Translational Sciences of the National Institutes of Health (NIH)U.S. governmentNational Institute of Child Health and Human DevelopmentNIHNational Center for Advancing Translational Sciences of the NIHU.S. Food and Drug AdministrationCempra PharmaceuticalsDuke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USADuke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USAKK Womens & Childrens Hosp, Childrens Intens Care Unit, Singapore, SingaporeUniv Fed Sao Paulo, Ecola Paulista Med, Div Neonatal Med, Sao Paulo, BrazilUniv N Carolina, Dept Pediat, Chapel Hill, NC USAMEDNAX Inc, Pediat Med Grp, Jacksonville, FL USAUniv Fed Sao Paulo, Ecola Paulista Med, Div Neonatal Med, Sao Paulo, BrazilNIH: UL1TR001117U.S. government: HHSN267200700051CNational Institute of Child Health and Human Development: K23HD068497National Institute of Child Health and Human Development: HHSN275201000003INational Institute of Child Health and Human Development: 1R01-HD081044-01National Center for Advancing Translational Sciences of the NIH: UL1TR001117U.S. Food and Drug Administration: 1R18-FD005292-01Cempra Pharmaceuticals: HHS0100201300009CWeb of Scienc

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants

To determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely-low-birth-weight (ELBW) infants

Taking forward a 'One Health' approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential.

The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a 'One Health' approach to control such zoonotic pathogens with epidemic potential

Renal cement embolism during percutaneous vertebroplasty

Percutaneous vertebroplasty (PVP) is an effective treatment for lesions of the vertebral body that involves a percutaneous injection of polymethylmethacrylate (PMMA). Although PVP is considered to be minimally invasive, complications can occur during the procedure. We encountered a renal embolism of PMMA in a 57-year-old man that occurred during PVP. This rare case of PMMA leakage occurred outside of the anterior cortical fracture site of the L1 vertebral body, and multiple tubular bone cements migrated to the course of the renal vessels via the valveless collateral venous network surrounding the L1 body. Although the authors could not explain the exact cause of the renal cement embolism, we believe that physicians should be aware of the fracture pattern, anatomy of the vertebral venous system, and careful fluoroscopic monitoring to minimize the risks during the PVP

High-Level Expression of Various Apolipoprotein (a) Isoforms by "Transferrinfection". The Role of Kringle IV Sequences in the Extracellular Association with Low-Density Lipoprotein

Characterization of the assembly of lipoprotein(a) [Lp(a)] is of fundamental importance to understanding the biosynthesis and metabolism of this atherogenic lipoprotein. Since no established cell lines exist that express Lp(a) or apolipoprotein(a) [apo(a)], a "transferrinfection" system for apo(a) was developed utilizing adenovirus receptor- and transferrin receptor-mediated DNA uptake into cells. Using this method, different apo(a) cDNA constructions of variable length, due to the presence of 3, 5, 7, 9, 15, or 18 internal kringle IV sequences, were expressed in cos-7 cells or CHO cells. All constructions contained kringle IV-36, which includes the only unpaired cysteine residue (Cys-4057) in apo(a). r-Apo(a) was synthesized as a precursor and secreted as mature apolipoprotein into the medium. When medium containing r-apo(a) with 9, 15, or 18 kringle IV repeats was mixed with normal human plasma LDL, stable complexes formed that had a bouyant density typical of Lp(a). Association was substantially decreased if Cys-4057 on r-apo(a) was replaced by Arg by site-directed mutagenesis or if Cys-4057 was chemically modified. Lack of association was also observed with r-apo(a) containing only 3, 5, or 7 kringle IV repeats without "unique kringle IV sequences", although Cys-4057 was present in all of these constructions. Synthesis and secretion of r-apo(a) was not dependent on its sialic acid content. r-Apo(a) was expressed even more efficiently in sialylation-defective CHO cells than in wild-type CHO cells. In transfected CHO cells defective in the addition of N-acetylglucosamine, apo(a) secretion was found to be decreased by 50%. Extracellular association with LDL was not affected by the carbohydrate moiety of r-apo(a), indicating a protein-protein interaction between r-apo(a) and apoB. These results show that, besides kringle IV-36, other kringle IV sequences are necessary for the extracellular association of r-apo(a) with LDL. Changes in the carbohydrate moiety of apo(a), however, do not affect complex formation

Randomized Controlled Trial of a Positive Affect Intervention to Reduce Stress in People Newly Diagnosed with HIV; Protocol and Design for the IRISS Study

Increasing evidence suggests that positive affect plays an important role in adaptation to chronic illness, independent of levels of negative affects like depression. Positive affect may be especially beneficial for people in the midst of severe stress, such as the diagnosis of human immunodeficiency virus (HIV). As medical treatments for HIV have improved, the number of people living with HIV has increased, and prevention strategies tailored specifically to people living with HIV have become a priority. There is a need for effective, creative, client-centered interventions that can be easily disseminated to community treatment settings, but there are currently few established interventions for people who are newly diagnosed with HIV. We present the design and methods for a randomized trial in which we test the efficacy of one such skills-based intervention that targets positive affect as a novel mechanism of change. The proposed research builds on observational findings of the important unique functions of positive affect. We aim to determine whether a five-session theory- and evidence-based intervention designed to teach skills for increasing the frequency and intensity of daily positive affect does so, and whether this intervention has beneficial effects on subsequent psychological well-being, health behaviors, and physical health up to 15 months after diagnosis with HIV. This is a randomized controlled trial in a sample of adults recruited within 12 weeks of testing positive for HIV. The control group is attention-matched, and follow up assessments will be conducted immediately post intervention (approximately 5 months post diagnosis) and at 10 and 15 months post diagnosis. This study is an important next step in research concerning the adaptive functions of positive affect for people coping with HIV or other health-related life stress