Browsing by Subject "Respiratory tract diseases"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    MicroRNA410 Inhibits Pulmonary Vascular Remodeling via Regulation of Nicotinamide Phosphoribosyltransferase
    (Springer Nature, 2019-07-09) Gao, Hui; Chen, Jiwang; Chen, Tianji; Wang, Yifang; Song, Yang; Dong, Yangbasai; Zhao, Shuangping; Machado, Roberto F.; Department of Medicine, IU School of Medicine
    Nicotinamide phosphoribosyltransferase (NAMPT) upregulation in human pulmonary artery endothelial cells (hPAECs) is associated with pulmonary arterial hypertension (PAH) progression and pulmonary vascular remodeling. The underlying mechanisms regulating NAMPT expression are still not clear. In this study, we aimed to study the regulation of NAMPT expression by microRNA410 (miR410) in hPAECs and explore the role of miR410 in the pathogenesis of experimental pulmonary hypertension. We show that miR410 targets the 3' UTR of NAMPT and that, concomitant with NAMPT upregulation, miR410 is downregulated in lungs of mice exposed to hypoxia-induced pulmonary hypertension (HPH). Our results also demonstrate that miR410 directly inhibits NAMPT expression. Overexpression of miR410 in hPAECs inhibits basal and VEGF-induced proliferation, migration and promotes apoptosis of hPAECs, while miR410 inhibition via antagomirs has the opposite effect. Finally, administration of miR410 mimics in vivo attenuated induction of NAMPT in PAECs and prevented the development of HPH in mice. Our results highlight the role of miR410 in the regulation of NAMPT expression in hPAECs and show that miR410 plays a potential role in PAH pathobiology by targeting a modulator of pulmonary vascular remodeling.
  • Thumbnail Image
    Item
    Regulating the adaptive immune response to respiratory virus infection
    (Springer Nature, 2012) Braciale, Thomas J.; Sun, Jie; Kim, Taeg S.; Pediatrics, IU School of Medicine
    Recent years have seen several advances in our understanding of immunity to virus infection of the lower respiratory tract, including to influenza virus infection. Here, we review the cellular targets of viruses and the features of the host immune response that are unique to the lungs. We describe the interplay between innate and adaptive immune cells in the induction, expression and control of antiviral immunity, and discuss the impact of the infected lung milieu on moulding the response of antiviral effector T cells. Recent findings on the mechanisms that underlie the increased frequency of severe pulmonary bacterial infections following respiratory virus infection are also discussed.
  • Thumbnail Image
    Item
    Safety of sildenafil in extremely premature infants: a phase I trial
    (Springer Nature, 2022-01) Jackson, Wesley; Gonzalez, Daniel; Smith, P. Brian; Ambalavanan, Namasivayam; Atz, Andrew M.; Sokol, Gregory M.; Hornik, Chi D.; Stewart, Dan; Mundakel, Gratias; Poindexter, Brenda B.; Ahlfeld, Shawn K.; Mills, Mary; Cohen-Wolkowiez, Michael; Martz, Karen; Hornik, Christoph P.; Laughon, Matthew M.; Pediatrics, School of Medicine
    Objective: To characterize the safety of sildenafil in premature infants. Study design: A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. Results: Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Conclusion: Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.
  • Thumbnail Image
    Item
    Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia
    (Springer Nature, 2019-09-30) Vyas-Read, Shilpa; Wymore, Erica M.; Zaniletti, Isabella; Murthy, Karna; Padula, Michael A.; Truog, William E.; Engle, William A.; Savani, Rashmin C.; Yallapragada, Sushmita; Logan, J. Wells; Zhang, Huayan; Hysinger, Erik B.; Grover, Theresa R.; Natarajan, Girija; Nelin, Leif D.; Porta, Nicolas F. M.; Potoka, Karin P.; DiGeronimo, Robert; Lagatta, Joanne M.; Children’s Hospitals Neonatal Consortium Severe BPD Focus Group; Pediatrics, School of Medicine
    Objective: To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). Study design: Infants with sBPD in the Children's Hospitals Neonatal Database who had echocardiograms 34-44 weeks' postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. Results: Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2-3.0; RVSP OR 2.2, 95% CI 1.1-4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. Conclusions: Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive.