Injection laryngoplasty with hyaluronic acid for glottal insufficiency in unilateral vocal fold paralysis: a systematic review of the literature.

BACKGROUND: Glottal insufficiency, mostly caused by unilateral vocal fold paralysis (UVFP) or vocal fold atrophy can be treated by injection laryngoplasty (IL). Materials such as hyaluronic acid (HA) gels are now widely available and used to improve voice quality. Various durability and effects of HA injection laryngoplasties have been reported. The aim of this study is to provide a systematic review of the literature for the use of HA in injection laryngoplasties. METHODS: A systematic literature search was conducted in PubMed and Cochrane Libraries. Three reviewers assessed original research studies concerning vocal fold augmentation with HA for eligibility. English written full-text human studies from 2000 to 2020 with EBM level 1b-2 were included. In vitro studies, animal studies, case reports, case-control studies, correspondence and review articles, and articles with other injection materials were excluded. Demographical data, indication, type of HA, evaluation methods, follow-up, durability of implanted material and complications were assessed. RESULTS: A total number of 311 articles were found in PubMed and Cochrane Library, 13 studies were eligible for final analysis with 1063 patients, mean age of patients was 58.7 years. Main indication for HA IL was unilateral vocal fold paralysis, evaluation methods were subjective-VHI (Voice Handicap Index) questionnaire and objective-acoustic and aerodynamic measurements, mean time of follow-up was 5.9 months. Large-particle HA gels were more favorable for longer durability than small-particle HA, reported time of resorption of HA gels ranges between 6 and 12 months, and complication rate was low. CONCLUSION: Hyaluronic acid injection laryngoplasty increases voice quality, improves results of voice therapy, and can be recommended as overlap treatment before permanent medialization surgery. Compared to other injected materials, HA seems to have more favorable effect on vibratory functions of the vocal folds and thus on the voice quality parameters.

Union of the European Phoniatricians' position statement on the exit strategy of phoniatric and laryngological services: staying safe and getting back to normal after the peak of coronavirus disease 2019 (issued on 25th May 2020).

BACKGROUND: The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services. OBJECTIVES: This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures. CONCLUSION: As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.

Oxidation as an important factor of protein damage: Implications for Maillard reaction.

Protein oxidation, the process caused especially by reactive oxygen and nitrogen species, is thought to play a major role in various oxidative processes within cells and is implicated in the development of many human diseases. This review provides a brief overview of the protein oxidation with the emphasis on the types of oxidation (oxidation of protein backbone and amino acid residues side chains, site-specific metal-catalysed protein oxidation), oxidationdependent generation of protein hydroperoxides, carbonyl derivatives and protein-protein cross-linkages. Nonenzymatic glycoxidation (also known as Maillard reaction) as an important factor of protein damage, consequences of oxidative protein impairment and related diseases as well as means of monitoring and assessment of protein modifications are discussed.

Changes of the complement system and rheological indicators after therapy with rheohemapheresis.

INTRODUCTION: In the last 10 years, many studies have been published on the role of the complement system in microcirculation disorders. However, as for the changes of complement components after rheohemapheresis, there is still a lack of detailed data in the literature. Complement changes may play an important role in pathogenesis of some microcirculation disorders, such as age-related macular degeneration and acute hearing loss. The objective of this study was to investigate the effect of rheohemapheresis on the basic complement pathways. PATIENTS AND METHODS: 32 patients were treated with rheohemapheresis, including 16 patients (10 men and 6 women) for age-related macular degeneration (AMD), mean age 69.7 ± 6.06 years (range 62-87 years) and 16 patients (11 men and 5 women) aged 56.4 ± 11.5 (range 34-73 years) for acute hearing loss. RESULTS: Rheohemapheresis led to a significant drop of all three complement-activation pathways in both groups of patients. Moreover, complement factor H was also reduced. CONCLUSION: The observed reduction in all three basic complement activation pathways after rheohemapheresis could be clinically important. The search continues both to find substances which influence complement systems and to develop more effective new drugs that require less frequent administration and that provide improved intraocular therapy for AMD patients.

Interaction of anthocyanins with drug-metabolizing and antioxidant enzymes.

Anthocyanins are generally considered to be the largest and the most important group of water-soluble pigments in plants. They are widely consumed by humans as natural compounds of vegetables, fruits, and red wine. Anthocyanins as well as other flavonoids show protective qualities against variety of pathologies, including cardiovascular diseases, cancer, diabetes mellitus, neurodegeneration, inflammation, viral infections, and obesity. Many healthy properties of anthocyanins are related to their antioxidant potency. Broad evidence of beneficial effects of anthocyanins on human health has led to their increasing popularity in the form of food supplements and nutraceuticals. As the nutraceuticals contain concentrated bioactive agents, consumed doses exceed those that could be obtained from food. Therefore, apart from anticipated improvement of human health it is essential to have in mind possible unexpected effects of anthocyanins. Interaction of these compounds with drug-metabolizing enzymes and transporters may affect the fate of co-administered drugs and thus exert pharmacological consequences. On the other hand, the modulation of certain drug-metabolizing and antioxidant enzymes by anthocyanins can contribute to chemoprotection and antioxidant defense of organisms. The present review summarizes anthocyanin properties with emphasis on the antioxidant capacity and deals with the potential of anthocyanins to modulate phase I and II drug-metabolizing enzymes, transporters and antioxidant enzymes. The undesirable and/or beneficial outcomes of possible interactions of anthocyanins with drugs or industrial pollutants are also discussed.

Evaluation of in vitro effects of natural substances of plant origin using a model of protein glycoxidation.

In an in vitro model with purified porcine aspartate aminotransferase (AST, EC 2.6.1.1) as the protein, the effects of phenolic antioxidants of plant origin (arbutin, methylarbutin, ferulic and isoferulic acids, o-coumaric and p-coumaric acids, quinic acid), flavonoids (baicalin and baicalein), and of hydroxycitric acid (HCA) at 0.5-50 mM concentration on the enzyme activities and on its glycation by 50 mM D-fructose as the glycating agent were studied. During incubation with AST at 37 degrees C up to 24 days, fructose alone decreased AST activities as a result of protein glycation. In the absence of fructose, 50 mM phenolic compounds gradually decreased AST activity, while no or a weak effect of individual compounds was found at 3 mM concentration. A direct negative effect on AST was pronounced with ferulic acid. On the other hand, beneficial influences of phenolic compounds on glycation of AST by fructose were found mostly at 3 mM concentration. Effects on glycation were vague at 50 mM concentration, probably due to a combination of direct negative influences and antiglycation effects of individual compounds. No effect, neither positive nor negative, on AST activity and protein glycation, was found with quinic acid. The flavonoid baicalin and its aglycon baicalein rapidly decreased the in vitro activity of the enzyme in all concentrations used (0.5-3 mM), and no beneficial effects of the compounds on glycation of the enzyme by fructose were found. The influence of HCA on glycation was concentration-depended, ranging from beneficial inhibition of glycation at 2.5 mM concentration to a strong decrease in AST activity at 10 mM HCA. Both the beneficial and undesirable effects of natural antioxidants should be considered in case they are used as antiglycation factors. The results obtained can contribute to the evaluation of quality of various generally recommended antioxidants.

[Enzyme inhibition in the drug therapy of benign prostatic hyperplasia]. / Inhibice enzymu ve farmakoterapii benigní hyperplazie prostaty.

Enzyme inhibition belongs to common mechanisms of drug action and enzymes of hormone metabolism belong to targets in the treatment of benign prostatic hyperplasia. Transformation of testosterone to 5 alpha-dihydrotestosterone is catalyzed by cholestenone-5 alpha-reductase (EC 1.3.1.22, 5 alpha-reductase). Different effects of dihydrotestosterone and testosterone represent a rational basis for pharmacotherapy by 5 alpha-reductase inhibition. The enzyme is active in the prostate and other organs and tissues, with different distribution of at least two 5 alpha-reductase isoenzymes. Beside this, progesterone-5 alpha-reductase (EC 1.3.1.30) as another enzyme with 5 alpha-reductase activity is present in human tissues including the prostate. The existence of several 5 alpha-reductase activities gives bright possibilities of 5 alpha-reductase inhibition. Basic 5 alpha-reductase inhibitors are synthetic steroid (e.g. finasteride--Proscar). Various mechanisms of their effect (classical reversible competitive inhibition, mechanism-based "suicide" inhibitors, tightly bound irreversible inhibitors...) represent different pharmacokinetic patterns, too. Non-steroidal 5 alpha-reductase inhibitors (e.g. polyunsaturated fatty acids) are effective components of several phytopharmaceuticals. They receive attention due to their complexity and low hazards. Extracts of Serenoa repens seeds (Permixon, Capistan in the Czech Republic), of Pygeum africanum, of Urtica radicis roots (Urtica, Urtiron) or catequine structures from the green tea belong to this group. Beside androgens, participation of estrogens in the origin and development of benign prostatic hyperplasia is probable. Inhibition of the "aromatase" complex, which catalyzes transformation of androgens to estrogens, may contribute to the complexity of phytotherapeutic effects.

Inhibitory effect of glycation on catalytic activity of alanine aminotransferase.

Non-enzymatic glycation is a common post-translational modification of tissue and plasma proteins which can impair their functions in living organisms. In this study, the authors have demonstrated for the first time an inhibitory effect of in vitro glycation on the catalytic activity of alanine aminotransferase (ALT, EC 2.6.1.2), a pyridoxal phosphate enzyme with several lysine residues in the molecule. The porcine heart enzyme was incubated with 50 mmol/l D-fructose, D-glucose, D,L-glyceraldehyde, or D-ribose in 0.1 mol/l phosphate buffer (pH 7.4) at 25 degrees C for up to 20 days. The strongest glycation effect was shown by D,L-glyceraldehyde, which caused complete enzyme inhibition within 6 days. After 20 days of incubation, the ALT activity in samples with D-fructose and D-ribose was less than 7% of the initial enzyme activity. A statistically significant effect of D-glucose on the enzymatic activity of ALT was not found. Incubation of ALT with D-fructose, D,L-glyceraldehyde and D-ribose minimized its catalytic activity both in the glycated and non-glycated fractions of the samples. Markedly higher activity was found in the glycated fraction with glucose. The inhibitory effect of glycation of ALT with D-fructose and D-ribose was found to be more intensive in the presence of L-alanine and weaker in the presence of 2-oxoglutarate. The findings suggest that glycation of the epsilon-amino group of Lys313 as a crucial part of the catalytic site of ALT may contribute to ALT inactivation in the presence of glycating sugars. Nevertheless, glycation of lysine residues outside the active center of ALT seems to be primary.

Influence of convulsants on rat brain activities of alanine aminotransferase and aspartate aminotransferase.

There exist differences between 12-day-old and adult rats in the onset of seizures induced by some inhibitors of glutamate decarboxylase (GAD). The aim of study was to investigate if there are differences between both groups in activities of rat brain alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the enzymes involved in glutamate metabolism, after the administration of 3-mercaptopropionic acid as specific GAD inhibitor or isoniazid as less specific general inhibitor of pyridoxal enzymes. Activities of both aminotransferases in a supernatant 20,000 g of the whole brain (containing predominantly cytosolic isoforms of enzymes) were increased at the beginning of 3-mercaptopropionic acid-induced generalized tonic-clonic seizures. At isoniazid-induced generalized tonic-clonic seizures, a significant increase in both enzyme activities was observed in adult rat brain. In the 12-day-old rat brain, ALT and AST activities reached about 40% and about 50-60% of adult control levels, respectively. In in vitro experiments, no influence of 3-mercaptopropionic acid on transaminase activities was found and an inhibitory effect of isoniazid on the enzymes was confirmed. Increased aminotransferase activities might participate in the enhanced synthesis of excitatory amino acid neurotransmitters in the nervous system, which may take a part in the initiation of epileptic seizures. Alternatively, the increased AST activity may be connected with an increased transport of NADH from the cytosol to mitochondria, while the increased ALT activity would represent the transformation of pyruvate to alanine as a consequence of increased glycolysis.

Metabolism of tryptophan in the liver: interference with decarboxylation of other aromatic amino acids.

Decarboxylation of aromatic amino acid in mammalian tissues is catalyzed by aromatic amino acid decarboxylase (EC. 4.1.1.28, AAD). The enzyme differs in its affinity to individual aromatic amino acids, the best substrates being 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytroptophan. Surprisingly, AAD is abundant in the liver, where the substrates with rather low affinity to AAD as tryptophan, phenylalanine, and tyrosine are offered to decarboxylation. In the present paper, the possibility of interference of tryptophan with decarboxylation of phenylalanine, tyrosine as well as dopa in the liver was investigated. The AAD activity was measured radiometrically with 1-14C-labeled aromatic amino acid substrates using the rat liver enzyme. The influence of tryptophan on decarboxylation of tyrosine was formally competitive with Ki = 9.2 x 10(-3) M, while the inhibition of decarboxylation of phenylalanine by tryptophan was non-competitive with Ki at 2.75 x 10(-2) M. The effect of tryptophan on decarboxylation of dopa was small and it could not be expressed in terms of inhibition kinetics and inhibition constant. At physiological concentrations of aromatic amino acids in plasma, tryptophan does not seem to have remarkable effects on decarboxylation of phenylalanine, tyrosine, and dopa in the liver.

Influence of stereoisomers of 4-fluoroglutamate on rat brain glutamate decarboxylase.

Inhibition of rat brain glutamate decarboxylase (GAD, EC 4.1.1.15) by individual stereoisomers of 4-fluoroglutamate (4-F-Glu) and 2-fluoro-4-aminobutyrate (2-F-GABA) was studied. All stereoisomers of 4-F-Glu inhibited decarboxylation of L-glutamate catalysed by the enzyme preparation. At 1 x 10(-2) M concentration, the most potent inhibitor of GAD was D-erythro-4-F-Glu with about 70% inhibition in the presence of 1.23 x 10(-2)M L-glutamate. The inhibition by all stereoisomers was of the competitive type. Ki values ranged from 2 x 10(-3)M for the D-erythro isomer to 1.1 x 10(-2)M for the D-threo and L-erythro isomers. The influence of all stereoisomers was reversible as shown by dialysis except for a small amount in the case of the D-erythro isomer. The inhibition was independent of external pyridoxal-5'-phosphate added. No inhibition of rat brain GAD was found with 2-fluoro-4-aminobutyrate stereoisomers.

[Relation between chemical structure and antimycobacterial activity against atypical strains. XIII. Thiosalicylanilides]. / Vztahy mezi chemickou strukturou látek a jejich antimykobakteriální aktivitou vuci atypickým kmenum XIII. Thiosalicylanilidy.

On the basis of a preliminary study of antimycobacterial activity of thiobenzanilides a series of eight thiosalicylanilides have been prepared. Synthetized compounds have been examined in vitro against Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium and Mycobacterium fortuitum. All compounds have been found very active. The values of minimal inhibitory concentrations are summarized in Table 1. 3',4'-Salicylanilide was selected for the following research. The compound have been found inactive in vivo (on experimental murine tuberculosis).

Inhibition of glutamate decarboxylase activity by 3-mercaptopropionic acid has different time course in the immature and adult rat brains.

It has been found that the latency of epileptic seizures caused by glutamate decarboxylase (GAD) inhibitor 3-mercaptopropionate (3-MPA) is markedly longer in immature rats than in the adults. Time course of rat brain GAD inhibition was studied in 12-day-old and adult (90-day-old) animals following 3-MPA (70 mg/kg i.p.). GAD activity was determined by quantification of 14CO2 liberated from [1-(14)C]glutamate by supernatant 20,000 x g of brain homogenate prepared from rats killed at different intervals after 3-MPA administration. In adult rats, the enzyme activity decreased significantly by 14.1% even 1 min after 3-MPA administration and was decreasing gradually till the onset of seizures. In immature rats, GAD activity decrease after 1 min was by 41.4% and further decrease was smaller. Comparison of the time profiles of GAD changes in both groups confirmed our findings that in spite of delayed seizure onset, GAD inhibition in immature rats is more pronounced, probably due to immaturity of the blood-brain barrier.

Influence of sanguinarine on the GABA synthesizing enzyme glutamate decarboxylase in vitro.

The inhibitory activity of the quaternary benzophenanthridine alkaloid sanguinarine on rat brain glutamate decarboxylase (GAD; EC 4.1.1.15) was studied in vitro. A value of Ki 7.10(-4) mol.1(-1) for sanguinarine was found. The inhibition was irreversible and increased during the preincubation time of sanguinarine with the GAD preparation. The results suggest that reaction of the iminium bond in the benzophenanthridine molecule with thiol groups of the enzyme participates in GAD inhibition. As GAD catalyzes the rate-limiting step of GABA synthesis, its inhibition by sanguinarine may contribute to its physiological action in vivo.

Sanguinarine and chelerythrine as inhibitors of aromatic amino acid decarboxylase.

Quaternary benzo[c]phenanthridine alkaloids sanguinarine, chelerythrine and their dihydroderivatives were tested as inhibitors of aromatic amino acid decarboxylase (EC 4.1, 1.28, AAD) from rat liver. Sanguinarine and chelerythrine exhibited strong inhibition of AAD with Ki 1.2 x 10(-4) M and 5.8 x 10(-4) M, respectively, while no inhibitory effect was observed for their dihydroderivatives. The inhibition was found to be irreversible. The enzyme-inhibitor interaction apparently stabilized AAD against thermal inactivation. Pyridoxal-5'-phosphate partially decreased but did not reverse the inhibition. Dithiothreitol prevented the inhibitory effect of sanguinarine and chelerythrine which indicates that the interaction with thiol groups essential for AAD activity is included in the inhibition mechanism.

Differences between immature and adult rats in brain glutamate decarboxylase inhibition by 3-mercaptopropionic acid.

Glutamate decarboxylase (EC 4.1.1.15, GAD) activity was studied in the brain of 12-day-old and adult rats treated with 3-mercaptopropionic acid (3-MPA), an inhibitor of GAD competitive with glutamate. Control GAD activity in the brains of immature animals (91.8 +/- 18.2 nmol/h/mg of protein) was lower than that of the adult rats (228 +/- 37.5 nmol/h/mg of protein). Brain GAD inhibition in adult rats was 58% at the onset of seizures (9 min on the average after administration of 70 mg 3-MPA/kg). At the same time, 3-MPA-treated young rats exhibited 76% inhibition of GAD despite the fact that at 9 min these animals were not yet having seizures. At the onset of seizures (19 min after 3-MPA on the average) their GAD activity remained at the same level. The difference between the groups was not related to the presence of the coenzyme pyridoxal-5'-phosphate in the enzyme assay. The inhibition of GAD by 3-MPA in vitro in the immature and adult brains was similar (Ki at 5.1 microM and 4.8 microM concentrations of 3-MPA, respectively). Identical values were found for Km of GAD (at 4.5 mM concentration of L-glutamate). Calculations based on the results suggest that 3-MPA enters the immature brain more easily than the brain of the adult animals. While GAD inhibition by 3-MPA is the primary cause of seizures, their onset is influenced by other factors, in which the immature brain differs from the adult one and which may include less sensitivity to GABA decrease due to relative overactivity of the GABA system.

Lack of inhibition of ornithine decarboxylase activity by ibuprofen.

The influence of the anti-inflammatory drug ibuprofen on the activity of ornithine decarboxylase (ODC, EC 4.1.1.17), the key enzyme of polyamine synthesis, was studied using a 20,000 g supernatant of rat testis and regenerating liver homogenates as sources of the enzyme. Ibuprofen, in all concentrations studied (10(-6) to 2 x 10(-3) M), did not influence either testicular or hepatic ODC activity in vitro. The role of ODC in inflammatory processes and the lack of ODC inhibition by ibuprofen are discussed in view of the controversial findings of other authors.

Inhibition of aromatic amino acid decarboxylase by a group of non-steroidal anti-inflammatory drugs.

In vitro inhibition of aromatic amino acid decarboxylase (AAD) by eight nonsteroidal anti-inflammatory drugs (NSAIDs) was studied. The most potent inhibitors were fenamates (IC50 for tolfenamate was 4.4 x 10(-5) M), while fluorinated biphenylic compounds (flobufen and 2',4'-difluorobiphenyl-4-yl acetate) and propionic acid derivatives (ibuprofen, ketoprofen, fenoprofen) were one order weaker. The in vitro inhibition of AAD by the compounds studied is probably not strong enough to contribute to their in vivo anti-inflammatory effects.