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Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity.

OBJECTIVES: To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS. STUDY DESIGN: Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed. RESULTS: All groups were comparable for birth weight and gestational age. Although the two random

Double-blind evaluation of developmental and health status to age 2 years of infants weighing 700 to 1350 grams treated prophylactically at birth with a single dose of synthetic surfactant or air placebo.

In a previously published article, we reported results of a two-center study of outcome to 28 days of 385 infants with birth weights from 700 to 1350 gm who were assigned randomly to receive a single 5 ml/kg intratracheal dose of either synthetic surfactant or air placebo. Infants treated with surfactant had a higher rate of survival to 28 days without bronchopulmonary dysplasia than did control subjects given an air placebo. The present study assessed survivors in early childhood to determine neurodevelopmental outcome and late morbidity. Two hundred fifty-eight surviving infants from both ce

Structural basis for the specific recognition of dual receptors by the homopolymeric pH 6 antigen (Psa) fimbriae of Yersinia pestis.

The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae that bind to two receptors: β1-linked galactosyl residues in glycosphingolipids and the phosphocholine group in phospholipids. Despite the ubiquitous presence of either moiety on the surface of many mammalian cells, Y. pestis appears to prefer interacting with certain types of human cells, such as macrophages and alveolar epithelial cells of the lung. The molecular mechanism of this apparent selectivity is not clear. Site-directed mutagenesis of the consensus choline-binding motif in the sequence of PsaA, the subunit of the Psa fim

Mumps virus can suppress the effective augmentation of HPC-induced apoptosis by IFN-gamma through disruption of IFN signaling in U937 cells.

Cells of the human promonocytic cell line U937 were found to be sensitive to hexadecylphosphocholine (HPC), which is a potential anticancer drug. Induction of apoptosis was found in U937 cells after treatment with HPC for 24 to 48 hr. The apoptosis in U937 cells exposed to HPC was increased significantly in the presence of interferon-gamma (IFN-gamma). The augmentation of HPC-induced apoptosis by IFN-gamma is repressed in cells (U937-MP) persistently infected with mumps virus. A persistently infected cell line, U937-MP, showed poor induction of signal transducers and activators of transcriptio

VAP-PLGA microspheres (VAP-PLGA) promote adipose-derived stem cells (ADSCs)-induced wound healing in chronic skin ulcers in mice via PI3K/Akt/HIF-1α pathway.

Chronic skin ulcers are a primary global health problem. Velvet antler polypeptide (VAP) regulates endothelial cell migration and angiogenic sprout. Adipose-derived stem cells (ADSCs) are reported to make pivotal impacts upon wound healing. This study aimed to explore the role of VAP combined with ADSCs in wound healing of chronic skin ulcers. The effect of VAP on phenotypes of ADSCs, and VAP (PLGA microspheres) combining with ADSCs on wound healing of chronic skin ulcers in vivo was evaluated. VAP generally promoted the proliferation, migration and invasion of ADSCs, and ADSC-induced angiogen

Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus.

We examined whether maternal dietary choline modulates angiogenesis in fetal brain. Pregnant C57BL/6 mice were fed either a choline-deficient (CD), control (CT), or choline-supplemented diet (CS) from days 12 to 17 (E12-17) of pregnancy and then fetal brains were studied. In CD fetal hippocampus, proliferation of endothelial cells (EC) was decreased by 32% (p < 0.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p < 0.01 vs. CT or CS). These changes were associated with > 25% decrease in the number of blood vessels in CD fetal hip

Synthetic surfactants: where are we? Evidence from randomized, controlled clinical trials.

The benefits of exogenous synthetic or animal-derived surfactants for prevention or treatment of respiratory distress syndrome (RDS) are well established. Data from head-to-head trials comparing animal-derived surfactants primarily with the synthetic surfactant colfosceril suggest that the major clinical advantages afforded by the presence of surfactant protein (SP)-B and SP-C in animal-derived preparations relate to faster onset of action, a reduction in the incidence of RDS when used prophylactically, and a lower incidence of air leaks and RDS-related deaths. However, no benefits in terms of

Oral combination of eugenol oleate and miltefosine induce immune response during experimental visceral leishmaniasis through nitric oxide generation with advanced cytokine demand.

Conventional therapy of visceral leishmaniasis (VL) remains challenging with the pitfall of toxicity, drug resistance, and expensive. Hence, urgent need for an alternative approach is essential. In this study, we evaluated the potential of combination therapy with eugenol oleate and miltefosine in Leishmania donovani infected macrophages and in the BALB/c mouse model. The interactions between eugenol oleate and miltefosine were found to be additive against promastigotes and amastigotes with xΣFIC 1.13 and 0.68, respectively. Significantly (p < 0.001) decreased arginase activity, increased nitr

Structure-Related Roles for the Conservation of the HIV-1 Fusion Peptide Sequence Revealed by Nuclear Magnetic Resonance.

Despite extensive characterization of the human immunodeficiency virus type 1 (HIV-1) hydrophobic fusion peptide (FP), the structure-function relationships underlying its extraordinary degree of conservation remain poorly understood. Specifically, the fact that the tandem repeat of the FLGFLG tripeptide is absolutely conserved suggests that high hydrophobicity may not suffice to unleash FP function. Here, we have compared the nuclear magnetic resonance (NMR) structures adopted in nonpolar media by two FP surrogates, wtFP-tag and scrFP-tag, which had equal hydrophobicity but contained wild-type

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1

Differences in immediate and short-term outcome of premature neonates treated with two types of exogenous surfactant preparation.

A retrospective review of the use of 2 types of exogenous surfactants was done to detect any differences in the short-term outcome. A total of 77 babies received surfactant replacement during the 1 year and 6 months under review. Of these, 30 had received a modified natural preparation, Survanta, and 47 had received a synthetic preparation, Exosurf. The median age at which the surfactant had been administered was at 4 hours of life. Twenty-three percent of all infants had received antenatal steroids. The infants who had received Survanta showed a more rapid initial response, with a lowering of

Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity.

Immunosenescence is associated with a decline in both T and B lymphocyte function. Although aged individuals have normal numbers of B cells in the periphery and are capable of mounting robust humoral responses, the antibodies produced are generally of lower affinity and are less protective than those produced by young animals. Here we review multiple studies that address the mechanisms that contribute to this decline. Taken together, these studies suggest that age-associated loss of the ability to generate protective humoral immunity results in part from reduced B lymphopoiesis. As the output

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… More recently, Cerny and colleagues [ 75 ] have extended these observations by demonstrating that antibodies produced by aged mice immunized with phosphorylcholine immunogens are not only of lower affinity and avidity but are also less protective against infection than those produced by young mice. … Phosphorylcholine antibody from young and aged mice differ in structure and protective activity against infection with Streptococcus pneumoniae J Immunol 1993 150 543 549 8419487 Miller C Kelsoe G Ig VH hypermutation is absent in the germinal centers of aged mice J Immunol 1995 155 3377 3384 7561032 …

Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antag

Molecular characterization of secretory proteins Rv3619c and Rv3620c from Mycobacterium tuberculosis H37Rv.

Rv3619c and Rv3620c are the secretory, antigenic proteins of the ESAT-6/CFP-10 family of Mycobacterium tuberculosis H37Rv. In this article, we show that Rv3619c interacts with Rv3620c to form a 1 : 1 heterodimeric complex with a dissociation constant (K(d)) of 4.8 × 10(-7) M. The thermal unfolding of the heterodimer was completely reversible, with a T(m) of 48 °C. The comparative thermodynamics and thermal unfolding analysis of the Rv3619c-Rv3620c dimer, the ESAT-6-CFP-10 dimer and another ESAT family heterodimer, Rv0287-Rv0288, revealed that the binding strength and stability of Rv3619c-Rv362

Perifosine inhibits S6K1-Gli1 signaling and enhances gemcitabine-induced anti-pancreatic cancer efficiency.

PURPOSE: The pancreatic cancer has extremely low overall 5-year survival, and gemcitabine is the only approved single agent for pancreatic cancer treatment. METHODS: In the present study, we investigated the potential effect of perifosine, a novel Akt inhibitor on gemcitabine-induced anti-pancreatic cancer effect both in vivo and in vitro. RESULTS: We showed that sub-cytotoxic low concentration of perifosine dramatically enhanced gemcitabine-induced cytotoxicity in cultured pancreatic cancer cells. Perifosine inhibited Akt-mammalian target of rapamycin and Erk-mitogen-activated protein kinas

Indomethacin pharmacodynamics are altered by surfactant: a possible challenge to current indomethacin dosing guidelines created before surfactant availability.

The effect of surfactant administration for respiratory distress syndrome (RDS) on indomethacin (INDO) pharmacodynamics and dosing requirements for patent ductus arteriosus (PDA) closure and renal toxicity was evaluated. A 22-year prospective cohort study including 442 INDO-treated patients given 466 INDO treatment courses. The database included demographic information, medical problems, and medications. Neonates with a PDA confirmed by echocardiography were treated with INDO, 0.25-0.3 mg/kg. Subsequent INDO dosing was based on a combined pharmacokinetic/pharmacodynamic (PK/PD) approach. Data

A Snapshot of Photoresponsive Liposomes in Cancer Chemotherapy and Immunotherapy: Opportunities and Challenges.

To provide precise medical regimens, photonics technologies have been involved in the field of nanomedicine. Phototriggered liposomes have been cast as promising nanosystems that achieve controlled release of payloads in several pathological conditions such as cancer, autoimmune, and infectious diseases. In contrast to the conventional liposomes, this photoresponsive element greatly improves therapeutic efficacy and reduces the adverse effects of gene/drug therapy during treatment. Recently, cancer immunotherpay has been one of the hot topics in the field of oncology due to the great success a

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… DSPC was used to self-assemble a zwitterionic polymer–lipid, poly(12-(methacryloyloxy)dodecyl phosphorylcholine), in a 1:4 molar ratio, which showed enhanced cytotoxicity on breast cancer cells through the release of ROS 65 ( Table 4 ). … liposome | DPPC, DSPEmPEG5k, AQ4N, and hCe6 | hCe6 (hexadecylamine-conjugated chlorin e6) | Balb/c mice bearing 4T1 tumors | PDT | improves the elimination of cancer in a mice model via sequential PDT and hypoxia-activated chemotherapy AQ4N | ( 67 ) zwitterionic liposomes | poly(12-methacryloyloxy)dodecyl phosphorylcholine …

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm.

This study aimed to assess the antitumour effects, molecular mechanisms of action, and potential synergy of ruxolitinib with sorafenib, KNK437, dasatinib, and perifosine, in Philadelphia-negative chronic myeloproliferative neoplasms (MPN). Cytotoxic and cytostatic effects of the different compounds were determined in the JAK2 V617F-positive cell lines, HEL and Ba/F3 (JAK2V617F EPOR) , and in primary mononuclear and bone marrow CD34-positive cells from 19 MPN patients. Ruxolitinib [50% inhibitory concentration (IC50 )(PV)  = 15 nmol/l], as well as sorafenib (IC50 PV=8μmol/l), KNK437 (IC50 PV=10

A Lecinoxoid, an oxidized phospholipid small molecule, constrains CNS autoimmune disease.

Oxidized phospholipids (Ox-PLs) are generated in abundance at sites of inflammation. Recent studies have indicated that Ox-PLs may also exhibit anti-inflammatory activities. In this study, we investigated the beneficial effect of VB-201, a pure synthetic Ox-PL analog that we synthesized, on the development of a central nervous system (CNS) autoimmune inflammatory disease, in vivo. Oral administration of VB-201 ameliorated the severity of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide MOG35-55, and restrained the encephalogenicity of