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European Annals of Otorhinolaryngology,... Sep 2021This review was conducted according to the Patient/problem Intervention Comparison Outcome (PICO) Statements. Some studies reported that 10-30% of patients consulting in... (Review)
Review
This review was conducted according to the Patient/problem Intervention Comparison Outcome (PICO) Statements. Some studies reported that 10-30% of patients consulting in ENT come with presenting symptoms of laryngopharyngeal reflux (LPR), but the exact prevalence of LPR is still unknown. Management has not changed in 20 years despite a significant increase in the number of publications on epidemiology, clinical presentation, diagnosis and treatment. The development of hypopharyngeal-esophageal multichannel intraluminal impedance pH monitoring (HEMII-pH) and saliva pepsin detection now allow a new multidimensional diagnostic approach associating clinical scores to HEMII-pH and saliva pepsin detection. This new approach may enable personalized treatment according to LPR profile on HEMII-pH (acid, non-acid, mixed; upright, recumbent reflux episodes). Updated treatment of LPR could consist in a 3-month association of dietary measures, proton pump inhibitors, alginate and magaldrate, followed by treatment adaptation.
Topics: Esophageal pH Monitoring; Humans; Hypopharynx; Laryngopharyngeal Reflux; Pepsin A; Saliva
PubMed: 33257265
DOI: 10.1016/j.anorl.2020.11.002 -
The Laryngoscope Jan 2023More than 20% of the US population suffers from laryngopharyngeal reflux. Although dietary/lifestyle modifications and alginates provide benefit to some, there is no...
OBJECTIVE
More than 20% of the US population suffers from laryngopharyngeal reflux. Although dietary/lifestyle modifications and alginates provide benefit to some, there is no gold standard medical therapy. Increasing evidence suggests that pepsin is partly, if not wholly, responsible for damage and inflammation caused by laryngopharyngeal reflux. A treatment specifically targeting pepsin would be amenable to local, inhaled delivery, and could prove effective for endoscopic signs and symptoms associated with nonacid reflux. The aim herein was to identify small molecule inhibitors of pepsin and test their efficacy to prevent pepsin-mediated laryngeal damage in vivo.
METHODS
Drug and pepsin binding and inhibition were screened by high-throughput assays and crystallography. A mouse model of laryngopharyngeal reflux (mechanical laryngeal injury once weekly for 2 weeks and pH 7 solvent/pepsin instillation 3 days/week for 4 weeks) was provided inhibitor by gavage or aerosol (fosamprenavir or darunavir; 5 days/week for 4 weeks; n = 3). Larynges were collected for histopathologic analysis.
RESULTS
HIV protease inhibitors amprenavir, ritonavir, saquinavir, and darunavir bound and inhibited pepsin with IC in the low micromolar range. Gavage and aerosol fosamprenavir prevented pepsin-mediated laryngeal damage (i.e., reactive epithelia, increased intraepithelial inflammatory cells, and cell apoptosis). Darunavir gavage elicited mild reactivity and no discernable protection; aerosol protected against apoptosis.
CONCLUSIONS
Fosamprenavir and darunavir, FDA-approved therapies for HIV/AIDS, bind and inhibit pepsin, abrogating pepsin-mediated laryngeal damage in a laryngopharyngeal reflux mouse model. These drugs target a foreign virus, making them ideal to repurpose. Reformulation for local inhaled delivery could further improve outcomes and limit side effects.
LEVEL OF EVIDENCE
NA. Laryngoscope, 133:S1-S11, 2023.
Topics: Animals; Mice; Laryngopharyngeal Reflux; Larynx; Pepsin A; Sulfonamides; Carbamates; Furans
PubMed: 35678265
DOI: 10.1002/lary.30242 -
Molecules (Basel, Switzerland) Aug 2023The lysozyme in the chicken egg white consists of various bioactive amino acids. However, these compounds are inactive when they are in the sequence of parent proteins....
The lysozyme in the chicken egg white consists of various bioactive amino acids. However, these compounds are inactive when they are in the sequence of parent proteins. They become active only when isolated from these proteins. The aim of this study was to modify lysozyme with proteolytic enzymes under specific conditions of the reaction environment so as to obtain active biopeptides. The physicochemical properties of the resulting preparations were also assessed. Our study showed that the modification of lysozyme with hydrolytic enzymes (pepsin and trypsin) under strictly specified conditions resulted in obtaining biopeptide preparations with new and valuable properties, as compared with native lysozyme. After the enzymatic modification of lysozyme, two structural fractions were distinguished in the composition of the resulting preparations-the monomeric fraction and the peptide fraction. The modified lysozyme exhibited high surface hydrophobicity and high total antibacterial activity despite the decrease in the hydrolytic activity. Modification of lysozyme with hydrolytic enzymes, especially pepsin, resulted in preparations with very good antioxidative properties.
Topics: Muramidase; Peptide Hydrolases; Pepsin A; Hydrolysis; Dermatologic Agents
PubMed: 37687089
DOI: 10.3390/molecules28176260 -
American Journal of Critical Care : An... Sep 2020Patients experience endotracheal intubation in various settings with wide-ranging risks for postintubation complications such as aspiration and ventilator-associated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients experience endotracheal intubation in various settings with wide-ranging risks for postintubation complications such as aspiration and ventilator-associated conditions.
OBJECTIVES
To evaluate associations between intubation setting, presence of aspiration biomarkers, and clinical outcomes.
METHODS
This study is a subanalysis of data from the NO-ASPIRATE single-blinded randomized clinical trial. Data were prospectively collected for 513 adult patients intubated within 24 hours of enrollment. Patients with documented aspiration events at intubation were excluded. In the NO-ASPIRATE trial, intervention patients received enhanced oropharyngeal suctioning every 4 hours and control patients received sham suctioning. Tracheal specimens for α-amylase and pepsin tests were collected upon enrollment. Primary outcomes were ventilator hours, lengths of stay, and rates of ventilator-associated conditions.
RESULTS
Of the baseline tracheal specimens, 76.4% were positive for α-amylase and 33.1% were positive for pepsin. Proportions of positive tracheal α-amylase and pepsin tests did not differ significantly between intubation locations (study hospital, transfer from other hospital, or field intubation). No differences were found for ventilator hours or lengths of stay. Patients intubated at another hospital and transferred had significantly higher ventilator-associated condition rates than did those intubated at the study hospital (P = .02). Ventilator-associated condition rates did not differ significantly between patients intubated in the field and patients in other groups.
CONCLUSIONS
Higher ventilator-associated condition rates associated with interhospital transfer may be related to movement from bed, vehicle loading and unloading, and transport vehicle vibrations. Airway assessment and care may also be suboptimal in the transport environment.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Intubation, Intratracheal; Length of Stay; Male; Middle Aged; Pepsin A; Prospective Studies; Respiratory Aspiration; Risk Factors; Single-Blind Method; Socioeconomic Factors; Suction; Trachea; alpha-Amylases
PubMed: 32869069
DOI: 10.4037/ajcc2020129 -
Journal of Dairy Science Feb 2022Hydrolysis-induced coagulation of casein micelles by pepsin occurs during the digestion of milk. In this study, the effect of pH (6.7-5.3) and pepsin concentration...
Hydrolysis-induced coagulation of casein micelles by pepsin occurs during the digestion of milk. In this study, the effect of pH (6.7-5.3) and pepsin concentration (0.110-2.75 U/mL) on the hydrolysis of κ-casein and the coagulation of the casein micelles in bovine skim milk was investigated at 37°C using reverse-phase HPLC, oscillatory rheology, and confocal laser scanning microscopy. The hydrolysis of κ-casein followed a combined kinetic model of first-order hydrolysis and putative pepsin denaturation. The hydrolysis rate increased with increasing pepsin concentration at a given pH, was pH dependent, and reached a maximum at pH ∼6.0. Both the increase in pepsin concentration and decrease in pH resulted in a shorter coagulation time. The extent of κ-casein hydrolysis required for coagulation was independent of the pepsin concentration at a given pH and, because of the lower electrostatic repulsion between para-casein micelles at lower pH, decreased markedly from ∼73% to ∼33% when pH decreased from 6.3 to 5.3. In addition, the rheological properties and the microstructures of the coagulum were markedly affected by the pH and the pepsin concentration. The knowledge obtained from this study provides further understanding on the mechanism of milk coagulation, occurring at the initial stage of transiting into gastric conditions with high pH and low pepsin concentration.
Topics: Animals; Caseins; Cattle; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Micelles; Milk Proteins; Pepsin A; Rheology
PubMed: 34998540
DOI: 10.3168/jds.2021-21177 -
Brazilian Journal of Otorhinolaryngology 2023Salivary pepsin has emerged as a biomarker for Laryngopharyngeal Reflux (LPR), which, however, has been questioned for its efficacy due to a lack of supporting medical... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Salivary pepsin has emerged as a biomarker for Laryngopharyngeal Reflux (LPR), which, however, has been questioned for its efficacy due to a lack of supporting medical data. Therefore, this study analyzed the diagnostic value of salivary pepsin for LPR and assessed a better cutoff value.
METHODS
Studies were searched in PubMed, Embase, and Cochrane Library from their receptions to October 1, 2021. Then, RevMan 5.3 and Stata 14.0 were utilized to summarize the diagnostic indexes for further meta-analysis. Data were separately extracted by two reviewers according to the trial data extraction form of the Cochrane Handbook. The risk of bias in Randomized Control Trials (RCTs) was evaluated with the Cochrane Risk of Bias Tool.
RESULTS
A total of 16 studies matched the criteria and were subjected to meta-analysis. The results revealed a pooled sensitivity of 61% (95% CI 50%-71%), a pooled specificity of 67% (95% CI 48%-81%), a positive likelihood ratio of 2 (95% CI 1.2-2.8), a negative likelihood ratio of 0.58 (95% CI 0.47‒0.72), and the area under the receiver operating characteristic curve of 0.67 (95% CI 0.63‒0.71). Subgroup analyses indicated that the cutoff value of pepsin at 50 ng/mL had a higher degree of diagnostic accuracy than that of pepsin at 16 ng/mL in cohort studies.
CONCLUSION
The review demonstrated low diagnostic performance of salivary pepsin for LPR and that the cutoff value of 50 ng/mL pepsin had superior diagnostic accuracy. Nevertheless, the diagnostic value may vary dependent on the utilized diagnostic criteria. Therefore, additional research is needed on the improved way of identifying salivary pepsin in the diagnosis of LPR, and also longer-term and more rigorous RCTs are warranted to further assess the effectiveness of salivary pepsin.
Topics: Humans; Laryngopharyngeal Reflux; Pepsin A; Saliva; ROC Curve; Biomarkers
PubMed: 36347787
DOI: 10.1016/j.bjorl.2022.10.050 -
European Archives of... Mar 2022We investigated the role of Glut-1 and H/K-ATPase expression in pepsin-induced development of human vocal cord leukoplakia cells (HVCLCs). Next, we analyzed the...
PURPOSE
We investigated the role of Glut-1 and H/K-ATPase expression in pepsin-induced development of human vocal cord leukoplakia cells (HVCLCs). Next, we analyzed the relationship between Glut-1 and H/K-ATPase expression with the clinicopathological features of laryngeal carcinoma.
METHODS
Glut-1 and H/K-ATPase expression levels in HVCLCs were determined after treatment with artificial gastric juice containing pepsin and laryngeal carcinoma tissues.
RESULTS
Exposure to pepsin-containing artificial gastric juice significantly enhanced the migration and proliferation of VSCLCs in a time-dependent manner. The apoptotic rate of VSCLCs decreased over time after exposure to pepsin and reached a nadir on day 7 (p < 0.01). With increasing duration of exposure to pepsin, the proportion of VSCLCs in G0/G1 phase decreased and the proportions in the S and G2/M phases significantly increased (p < 0.05). After treatment with pepsin-containing artificial gastric juice, RT-PCR and Western blotting showed that the expression of Glut-1 and H/K-ATPase α, β significantly increased in HVCLCs compared to in the absence of pepsin (p < 0.05). The expression of Glut-1 and H/K-ATPase α, β gradually increased from vocal cord leukoplakia (VLC) to laryngeal carcinoma (p < 0.05). Lentivirus-mediated inhibition of Glut-1 expression in VCL significantly inhibited the cells' migration and proliferation (p < 0.05) but enhanced their apoptosis (p < 0.05). Also, inhibition of Glut-1 expression resulted in an increased proportion of cells in G0/G1 phase and a significantly decreased proportion in G2/M phase (p < 0.05).
CONCLUSIONS
Elevated Glut-1 expression may promote the development of VCL by upregulating laryngeal H/K-ATPase expression to reactivate absorbed pepsin, thus damaging the laryngeal mucosa.
Topics: Adenosine Triphosphatases; Glucose Transporter Type 1; H(+)-K(+)-Exchanging ATPase; Humans; Laryngeal Neoplasms; Laryngopharyngeal Reflux; Leukoplakia; Pepsin A; Vocal Cords
PubMed: 34800155
DOI: 10.1007/s00405-021-07172-y -
International Journal of Biological... Jun 2022Pepsin is a protease used in many different applications, and in many instances, it is utilized in an immobilized form to prevent contamination of the reaction product.... (Review)
Review
Pepsin is a protease used in many different applications, and in many instances, it is utilized in an immobilized form to prevent contamination of the reaction product. This enzyme has two peculiarities that make its immobilization complex. The first one is related to the poor presence of primary amino groups on its surface (just one Lys and the terminal amino group). The second one is its poor stability at alkaline pH values. Both features make the immobilization of this enzyme to be considered a complicated goal, as most of the immobilization protocols utilize primary amino groups for immobilization. This review presents some of the attempts to get immobilized pepsin biocatalyst and their applications. The high density of anionic groups (Asp and Glu) make the anion exchange of the enzyme simpler, but this makes many of the strategies utilized to immobilize the enzyme (e.g., amino-glutaraldehyde supports) more related to a mixed ion exchange/hydrophobic adsorption than to real covalent immobilization. Finally, we propose some possibilities that can permit not only the covalent immobilization of this enzyme, but also their stabilization via multipoint covalent attachment.
Topics: Enzyme Stability; Enzymes, Immobilized; Glutaral; Hydrogen-Ion Concentration; Pepsin A
PubMed: 35508226
DOI: 10.1016/j.ijbiomac.2022.04.224 -
European Archives of... Jun 2022Laryngopharyngeal reflux disease (LPRD) is a general term for the reflux of gastroduodenal contents into the laryngopharynx, oropharynx and even the nasopharynx, causing... (Review)
Review
PURPOSE
Laryngopharyngeal reflux disease (LPRD) is a general term for the reflux of gastroduodenal contents into the laryngopharynx, oropharynx and even the nasopharynx, causing a series of symptoms and signs. Currently, little is known regarding the physiopathology of LPRD, and proton pump inhibitors (PPIs) are the drugs of choice for treatment. Although acid reflux plays a critical role in LPRD, PPIs fail to relieve symptoms in up to 40% of patients with LPRD. The influence of other reflux substances on LPRD, including pepsin, bile acid, and trypsin, has received increasing attention. Clarification of the substances involved in LPRD is the basis for LPRD treatment.
METHODS
A review of the effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases was conducted in PubMed.
RESULTS
Different reflux substances have different effects on LPRD, which will cause various symptoms, inflammatory diseases and neoplastic diseases of the laryngopharynx. For LPRD caused by different reflux substances, 24-h multichannel intraluminal impedance combined with pH-metry (MII-pH), salivary pepsin, bile acid and other tests should be established so that different drugs and treatment courses can be used to provide patients with more personalized treatment plans.
CONCLUSION
This article summarizes the research progress of different reflux substances on the pathogenesis, detection index and treatment of LPRD and lays a theoretical foundation to develop target drugs and clinical diagnosis and treatment.
Topics: Bile Acids and Salts; Esophageal pH Monitoring; Humans; Laryngopharyngeal Reflux; Pepsin A; Proton Pump Inhibitors; Trypsin
PubMed: 34860271
DOI: 10.1007/s00405-021-07201-w -
Marine Drugs Feb 2023There is a growing demand for the identification of alternative sources of collagen not derived from land-dwelling animals. The present study explored the use of pepsin-...
There is a growing demand for the identification of alternative sources of collagen not derived from land-dwelling animals. The present study explored the use of pepsin- and acid-based extraction protocols to isolate collagen from the swim bladders of . After extraction, these acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) samples respectively were subjected to spectral analyses and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) characterization, revealing both to be comprised of type I collagen with a triple-helical structure. The imino acid content of these ASC and PSC samples was 195 and 199 residues per 1000 residues, respectively. Scanning electron microscopy demonstrated that samples of freeze-dried collagen exhibited a compact lamellar structure, while transmission electron microscopy and atomic force microscopy confirmed the ability of these collagens to undergo self-assembly into fibers. ASC samples exhibited a larger fiber diameter than the PSC samples. The solubility of both ASC and PSC was highest under acidic pH conditions. Neither ASC nor PSC caused any cytotoxicity when tested in vitro, which met one of the requirements for the biological evaluation of medical devices. Thus, collagen isolated from the swim bladders of holds great promise as a potential alternative to mammalian collagen.
Topics: Animals; Pepsin A; Fish Proteins; Collagen; Collagen Type I; Acids; Perciformes; Solubility; Skin; Mammals
PubMed: 36976208
DOI: 10.3390/md21030159