scholarly journals Aviptadil: Class Effect of a Synthetic Vasoactive Intestinal Peptide as a Treatment Option in Patients with COVID-19 with Severe Respiratory Failure

2022 ◽  
Author(s):  
Dwaipayan Sarathi Chakraborty ◽  
Shouvik Choudhury ◽  
Sandeep Lahiry
Keyword(s):  
Respiratory Failure ◽  
Vasoactive Intestinal Peptide ◽  
Vaccine Development ◽  
Treatment Options ◽  
Structural Protein ◽  
Class Effect ◽  
Lung Protection ◽  
Proinflammatory Mediators ◽  
Effective Option ◽  
Lung Injuries

Despite dynamic drug and vaccine development processes to reduce the disease burden of COVID-19, the treatment options are still very limited. Vasoactive intestinal peptide (VIP) has a diversified physiological action with specific features of lung protection-related activities. VIP inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gene replication in human monocytes and the viral replication in Calu-3 cells, thus further reducing the generation of proinflammatory mediators. Aviptadil, a synthetic form of VIP, is the only pulmonary therapeutic agent to have been granted ‘fast track’ status by the U.S. Food and Drug Administration (FDA) and to be allowed into both Phase II and III clinical trials. Initial binding of Aviptadil with non-structural protein (nsp) 10 and nsp16, which may inhibit the 2’-O-methyltransferase activity of the SARS-CoV-2 nsp10 and nsp16 complex. Aviptadil has already proved to be an effective option in the treatment of severe respiratory failures due to sepsis and other related lung injuries. Interim analysis results of this drug used in respiratory failure caused by SARS-CoV-2 has evolved a new hope in regard to safety and efficacy. The final results from a recently completed trial, as well as all currently ongoing trials, will clarify the class effect of this drug in the treatment of COVID-19 in future days.

scholarly journals A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raymond J. Langley ◽  
Marie E. Migaud ◽  
Lori Flores ◽  
J. Will Thompson ◽  
Elizabeth A. Kean ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Patient Outcomes ◽  
Medical Intensive Care Unit ◽  
Close Association ◽  
Treatment Options ◽  
Feature Model ◽  
High Morbidity ◽  
Medical Intensive Care ◽  
Poor Outcomes

AbstractAcute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition.

scholarly journals Successful endovascular stenting of a bleeding external iliac vein mycotic aneurysm in an oncologic patient: a case report

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Rupal S. Parikh ◽  
Shiyi Li ◽  
Christopher Shackles ◽  
Tamim Khaddash
Keyword(s):  
Mycotic Aneurysm ◽  
Case Reports ◽  
Treatment Options ◽  
Iliac Vein ◽  
Pelvic Abscess ◽  
Vascular Lesions ◽  
Endovascular Stenting ◽  
Oncologic Patient ◽  
External Iliac Vein ◽  
Effective Option

Abstract Background Mycotic aneurysms are rare vascular lesions, occurring in 0.6–2% of arterial aneurysms but with no reported venous cases. Venous aneurysms unrelated to an underlying infectious process have been previously described and are typically surgically repaired due to risk of thromboembolic events. Case presentation This case reports a bleeding external iliac vein mycotic aneurysm secondary to erosion of a chronic pelvic abscess, successfully treated with endovascular stenting, in an oncologic patient without alternative therapeutic options. Conclusion Venous aneurysms are uncommon vascular lesions which have historically been treated with open surgical repair. Given the lower degree of procedural morbidity, endovascular management of these lesions may be an effective option in the appropriate setting, particularly as a last resort in patients without surgical treatment options.

scholarly journals Protection againstStaphylococcus aureusColonization and Infection by B- and T-Cell-Mediated Mechanisms

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Fan Zhang ◽  
Olivia Ledue ◽  
Maria Jun ◽  
Cibelly Goulart ◽  
Richard Malley ◽  
...  
Keyword(s):  
T Cell ◽  
Soft Tissue ◽  
Bacterial Infections ◽  
Vaccine Development ◽  
Pathological Condition ◽  
Treatment Options ◽  
Immune Defense ◽  
Invasive Infection ◽  
Content Type ◽  
Increased Risk

ABSTRACTStaphylococcus aureusis a major cause of morbidity and mortality worldwide.S. aureuscolonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management.S. aureusvaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by anS. aureusvaccine in protection againstS. aureusbacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-inducedS. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality duringS. aureusbacteremia, whereas Th1 or Th17 responses are essential for prevention ofS. aureusskin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention ofS. aureusdermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses toS. aureusantigens may be critical to achieve effective and comprehensive immune defense against this pathogen.IMPORTANCES. aureusis a leading cause of healthcare- and community-associated bacterial infections.S. aureuscauses various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections.S. aureuscolonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development againstS. aureushas been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses toS. aureusantigens in conferring enhanced and broad protection againstS. aureusinvasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.

scholarly journals Treatment of Toxoplasmosis and Neosporosis in Farm Ruminants: State of Knowledge and Future Trends

2018 ◽  
Vol 18 (15) ◽  
pp. 1304-1323 ◽  
Author(s):  
Roberto Sánchez-Sánchez ◽  
Patricia Vázquez ◽  
Ignacio Ferre ◽  
Luis Miguel Ortega-Mora
Keyword(s):  
Vaccine Development ◽  
Neospora Caninum ◽  
Treatment Options ◽  
Small Ruminants ◽  
Additional Treatment ◽  
Current Status ◽  
Caninum Infection ◽  
Zoonotic Parasites ◽  
Toxoplasma Gondii Infection

Toxoplasmosis and neosporosis are closely related protozoan diseases that lead to important economic impacts in farm ruminants. Toxoplasma gondii infection mainly causes reproductive failure in small ruminants and is a widespread zoonosis, whereas Neospora caninum infection is one of the most important causes of abortion in cattle worldwide. Vaccination has been considered the most economic measure for controlling these diseases. However, despite vaccine development efforts, only a liveattenuated T. gondii vaccine has been licensed for veterinary use, and no promising vaccines against neosporosis have been developed; therefore, vaccine development remains a key goal. Additionally, drug therapy could be a valuable strategy for disease control in farm ruminants, as several drugs that limit T. gondii and N. caninum proliferation and dissemination have been evaluated. This approach may also be relevant to performing an initial drug screening for potential human therapy for zoonotic parasites. Treatments can be applied against infections in adult ruminants to minimize the outcomes of a primo-infection or the reactivation of a chronic infection during gestation or in newborn ruminants to avoid infection chronification. In this review, the current status of drug development against toxoplasmosis and neosporosis in farm ruminants is presented, and in an effort to promote additional treatment options, prospective drugs that have shown efficacy in vitro and in laboratory animal models of toxoplasmosis and neosporosis are examined.

Alternative Modes of Mechanical Ventilation

2018 ◽  
Vol 29 (4) ◽  
pp. 396-404
Author(s):  
John J. Gallagher
Keyword(s):  
Mechanical Ventilation ◽  
Closed Loop ◽  
Treatment Options ◽  
Ventilatory Support ◽  
Dual Control ◽  
Mechanical Ventilators ◽  
Lung Protection ◽  
Ventilation Modes ◽  
Volume Controlled ◽  
Pressure Controlled

Modern mechanical ventilators are more complex than those first developed in the 1950s. Newer ventilation modes can be difficult to understand and implement clinically, although they provide more treatment options than traditional modes. These newer modes, which can be considered alternative or nontraditional, generally are classified as either volume controlled or pressure controlled. Dual-control modes incorporate qualities of pressure-controlled and volume-controlled modes. Some ventilation modes provide variable ventilatory support depending on patient effort and may be classified as closed-loop ventilation modes. Alternative modes of ventilation are tools for lung protection, alveolar recruitment, and ventilator liberation. Understanding the function and application of these alternative modes prior to implementation is essential and is most beneficial for the patient.

scholarly journals Countermeasures to Coronavirus Disease 2019: Are Immunomodulators Rational Treatment Options—A Critical Review of the Evidence

2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Daniel B Chastain ◽  
Tia M Stitt ◽  
Phong T Ly ◽  
Andrés F Henao-Martínez ◽  
Carlos Franco-Paredes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Failure ◽  
Distress Syndrome ◽  
Treatment Options ◽  
Immune Dysregulation ◽  
Lung Damage ◽  
Safety And Efficacy ◽  
Rational Treatment ◽  
Immunomodulatory Therapies

Abstract Severe acute respiratory syndrome coronavirus 2 is associated with higher concentrations of proinflammatory cytokines that lead to lung damage, respiratory failure, and resultant increased mortality. Immunomodulatory therapy has the potential to inhibit cytokines and quell the immune dysregulation. Controversial data found improved oxygenation after treatment with tocilizumab, an interleukin-6 inhibitor, sparking a wave of interest and resultant clinical trials evaluating immunomodulatory therapies. The purpose of this article is to assess potential proinflammatory targets and review the safety and efficacy of immunomodulatory therapies in managing patients with acute respiratory distress syndrome associated with coronavirus disease 2019.

scholarly journals Capsid Assembly is Regulated by Amino Acid Residues Asparagine 47 and 48 in The VP2 Protein of Porcine Parvovirus

2020 ◽  
Author(s):  
Jucai Wang ◽  
Yunchao Liu ◽  
Yumei Chen ◽  
Teng Zhang ◽  
Aiping Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Vaccine Development ◽  
Acid Sites ◽  
Site Directed Mutagenesis ◽  
Porcine Parvovirus ◽  
Capsid Assembly ◽  
Structural Protein ◽  
Native Page ◽  
Vp2 Protein

Abstract Background: Porcine parvovirus (PPV) is a major cause of reproductive failure in swine, and has caused huge losses throughout the world. Viral protein 2 (VP2) of PPV is a major structural protein that can self-assemble into virus-like particles (VLP) with hemagglutination (HA) activity. In order to identify the essential residues involved in the mechanism of capsid assembly and to further understand the function of HA, we analyzed a series of deletion mutants and site-directed mutations within the N-terminal of VP2 in the Escherichia coli (E. coli) system. Results: Our results showed that deletion of first 47 amino acids from the N-terminal of VP2 protein did not affect capsid assembly, and further truncation to residue 48 Asparagine (Asn, N) caused detrimental effects. Site-directed mutagenesis experiments demonstrated that residue 47Asn reduced the assembly efficiency of PPV VLP, while residue 48Asn destroyed the stability, hemagglutination, and self-assembly characteristics of the PPV VP2 protein. These findings indicated that the residues 47Asn and 48Asn are important amino acid sites to capsid assembly and HA activity. Results from Native PAGE inferred that macromolecular polymers were critical intermediates of the VP2 protein during the capsid assembly process. Site-directed mutation at 48Asn did not affect the association of monomers to form into oligomers, but destroyed the ability of oligomers to assemble into macromolecular particles, influencing both capsid assembly and HA activity. Conclusions: These results demonstrated that PPV capsid assembly is a complex process that is regulated by amino acids 47Asn and 48Asn, which are located at the N-terminal of VP2 and closely related to the association of macromolecular particles. Our findings provide valuable information on the mechanisms of PPV capsid assembly and the possibility of chimeric VLP vaccine development by replacing as much as 47 amino acids at the N-terminal of VP2 protein.

scholarly journals Whole Genome Sequence Analysis and Homology Modelling of a 3C Like Peptidase and a Non-Structural Protein 3 of the SARS-CoV-2 Shows Protein Ligand Interaction with an Aza-Peptide and a Noncovalent Lead Inhibitor with Possible Antiviral Properties

2020 ◽  
Author(s):  
Arun Shanker ◽  
Divya Bhanu ◽  
Anjani Alluri
Keyword(s):  
Amino Acids ◽  
Binding Sites ◽  
Tertiary Structure ◽  
Vaccine Development ◽  
Homology Modelling ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Structural Protein ◽  
Ligand Interaction ◽  
Percent Identity

<p></p><p>The family of viruses belonging to Coronaviridae mainly consist of virulent pathogens that have a zoonotic property, Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) of this family have emerged before and now the SARS-CoV-2 has emerged in China. Characterization of spike glycoproteins, polyproteins and other viral proteins from viruses are important for vaccine development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand binding sites and explore the possible antiviral properties of these protein ligand complexes. Any information emerging from these protein models can be used for vaccine development. In this study we did a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and homology modelling of the <a>SARS-CoV-2 </a>whole genome sequences, the spike protein and the polyproteins for homology with known proteins, we also analysed receptor binding sites in these models for possible binding with ligands that exhibit antiviral properties. Our results showed that the tertiary structure of the polyprotein isolate SARS-CoV-2_HKU-SZ-001_2020 had 98.94 percent identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors. <a>Our results indicate that a part of the viral genome </a><a>(residues 3268 -3573 in Frame 2 with 306 amino acids) of the SARS-CoV-2 virus isolate Wuhan-Hu-1 (Genbank Accession Number MN908947.3) </a>when modelled with template 2a5i of the PDB database had 96 percent identity with a 3C like peptidase of SARS-CoV which has ability to bind with Aza-Peptide Epoxide (APE) which is known for irreversible inhibition of SARS-CoV main peptidase. The part of the genome (residues 1568-1882 in Frame 2 with 315 amino acids) when modelled with template 3e9s of the PDB database had 82 percent identity with a papain-like protease/deubiquitinase which when complexed with ligand GRL0617 acts as inhibitor which can block SARS-CoV replication. The regions studied was conserved in more than 90 genomes of SARS-CoV-2. It is possible that these viral inhibiters can be used for vaccine development for the SARS-CoV-2.</p><p></p><p></p>

Soil aquifer treatment using advanced primary effluent

2011 ◽  
Vol 64 (3) ◽  
pp. 640-646 ◽  
Author(s):  
Saroj K. Sharma ◽  
Mustefa Hussen ◽  
Gary Amy
Keyword(s):  
Wastewater Treatment ◽  
Soil Column ◽  
Treatment Options ◽  
Suspended Solid ◽  
Head Loss ◽  
Soil Aquifer Treatment ◽  
Effective Option ◽  
Attractive Option ◽  
Pre Treatment ◽  
Sedimentation Basins

Soil aquifer treatment (SAT) using primary effluent (PE) is an attractive option for wastewater treatment and reuse in many developing countries with no or minimal wastewater treatment. One of the main limitations of SAT of PE is rapid clogging of the infiltration basin due to high suspended solid concentrations. Some pre-treatment of PE before infiltration is likely to reduce this limitation, improve performance of SAT and help to implement this technology effectively. The effects of three pre-treatment options namely sedimentation (SED), coagulation (COAG) and horizontal roughing filtration (HRF) on SAT were analyzed by conducting laboratory-scale batch and soil column experiments. The sedimentation and coagulation pre-treatments led to less head loss development and reduction of clogging effect. The head loss development in soil column using PE + COAG and PE + SED was reduced by 85 and 72%, respectively, compared to PE alone without any pre-treatment. The overall dissolved organic carbon (DOC) removal of pre-treatments and soil column collectively were 34, 44, 51 and 43.5% for PE without any pre-treatment, PE + SED, PE + COAG and PE + HRF, respectively. Coagulation pre-treatment of PE was found to be the most effective option in terms of suspended solids, DOC and nitrogen removal. Sedimentation pre-treatment of PE could be attractive where land is relatively less expensive for the construction of sedimentation basins.

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