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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 -
Otolaryngologia Polska = the Polish... Dec 2017Laryngopharyngeal reflux (LPR) is a common defect among laryngological and phoniatric patients. Although LPR is categorized as a superficial gastroesophageal reflux... (Review)
Review
Laryngopharyngeal reflux (LPR) is a common defect among laryngological and phoniatric patients. Although LPR is categorized as a superficial gastroesophageal reflux disease (GERD), differential diagnosis should treat these two diseases separately. LPR symptoms can be assessed in the interview using as a tool the reflux symptom index (RSI). In addition, changes in the larynx that occur during LPR might be seen during laryngoscopy and classified according to the reflux finding score (RFS). One of the main mucosal irritants in LPR is pepsin which digests proteins and impairs the functions of the upper respiratory tract cells by affecting carbonate anhydrase (CAIII) and the Sep 70 protein. Pepsin initiates inflammatory changes within the larynx, nasopharynx and nasal cavity. The use of pepsin detection in upper and lower throat secretions is a new direction in LPR diagnostics.
Topics: Adult; Aged; Aged, 80 and over; Female; Gastrointestinal Agents; Humans; Laryngopharyngeal Reflux; Larynx; Male; Middle Aged; Pepsin A
PubMed: 29327685
DOI: 10.5604/01.3001.0010.7194 -
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 -
Nutrients Oct 2022The current bibliometric review evaluated recent papers that researched dietary protein sources to generate antidiabetic bioactive peptides/hydrolysates for the... (Review)
Review
The current bibliometric review evaluated recent papers that researched dietary protein sources to generate antidiabetic bioactive peptides/hydrolysates for the management of diabetes. Scopus and PubMed databases were searched to extract bibliometric data and, after a systematic four-step process was performed to select the articles, 75 papers were included in this review. The countries of origin of the authors who published the most were China (67%); Ireland (59%); and Spain (37%). The journals that published most articles on the subject were Food Chemistry (n = 12); Food & Function (n = 8); and Food Research International (n = 6). The most used keywords were 'bioactive peptides' (occurrence 28) and 'antidiabetic' (occurrence 10). The most used enzymes were Alcalase (17%), Trypsin (17%), Pepsin, and Flavourzyme (15% each). It was found that different sources of protein have been used to generate dipeptidyl peptidase IV (DPP-IV), α-amylase, and α-glucosidase inhibitory peptides. In addition to antidiabetic properties, some articles (n = 30) carried out studies on multifunctional bioactive peptides, and the most cited were reported to have antioxidant and antihypertensive activities (n = 19 and 17, respectively). The present review intended to offer bibliometric data on the most recent research on the production of antidiabetic peptides from dietary proteins to those interested in their obtention to act as hypoglycemic functional ingredients. The studies available in this period, compiled, are not yet enough to point out the best strategies for the production of antidiabetic peptides from food proteins and a more systematic effort in this direction is necessary to allow a future scale-up for the production of these possible functional ingredients.
Topics: Dipeptidyl Peptidase 4; Hypoglycemic Agents; Dipeptidyl-Peptidase IV Inhibitors; alpha-Glucosidases; Pepsin A; Antioxidants; Trypsin; Antihypertensive Agents; Peptides; alpha-Amylases; Subtilisins; Dietary Proteins; Bibliometrics
PubMed: 36296965
DOI: 10.3390/nu14204275 -
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