The Role of Glutathione in Selected Viral Diseases.

During inflammatory processes, immunocompetent cells are exposed to substantial amounts of free radicals and toxic compounds. Glutathione is a cysteine-containing tripeptide that is an important and ubiquitous antioxidant molecule produced in human organs. The intracellular content of GSH regulates the detoxifying capacity of cells, as well as the inflammatory and immune response. GSH is particularly important in the liver, where it serves as the major non-protein thiol involved in cellular antioxidant defense. There are numerous causes of hepatitis. The inflammation of the liver can be caused by a variety of infectious viruses. The relationship between oxidative stress and the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV) infection is not fully known. The aim of this study was to examine the relationship between hepatotropic viruses and glutathione status, including reduced glutathione (GSH) and oxidized glutathione (GSSG), as well as antioxidant enzymes, e.g., glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) in liver diseases.

The Role of Oxidative Stress Enhanced by Adiposity in Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs), including cardiovascular disease (CVD), metabolic syndrome (MetS), and type 2 diabetes (T2D), are associated with increased morbidity and mortality. The growing prevalence of CVD is mostly attributed to the aging population and common occurrence of risk factors, such as high systolic blood pressure, elevated plasma glucose, and increased body mass index, which led to a global epidemic of obesity, MetS, and T2D. Oxidant-antioxidant balance disorders largely contribute to the pathogenesis and outcomes of CMDs, such as systemic essential hypertension, coronary artery disease, stroke, and MetS. Enhanced and disturbed generation of reactive oxygen species in excess adipose tissue during obesity may lead to increased oxidative stress. Understanding the interplay between adiposity, oxidative stress, and cardiometabolic risks can have translational impacts, leading to the identification of novel effective strategies for reducing the CMDs burden. The present review article is based on extant results from basic and clinical studies and specifically addresses the various aspects associated with oxidant-antioxidant balance disorders in the course of CMDs in subjects with excess adipose tissue accumulation. We aim at giving a comprehensive overview of existing knowledge, knowledge gaps, and future perspectives for further basic and clinical research. We provide insights into both the mechanisms and clinical implications of effects related to the interplay between adiposity and oxidative stress for treating and preventing CMDs. Future basic research and clinical trials are needed to further examine the mechanisms of adiposity-enhanced oxidative stress in CMDs and the efficacy of antioxidant therapies for reducing risk and improving outcome of patients with CMDs.

Nickel ions influence the transepithelial sodium transport in the trachea, intestine and skin.

Measurements of transepithelial potential and resistance in tissue and organ model systems enable the evaluation of the Ni2+ effect on the epithelial sodium channels, aquaporin 3, and the sodium-potassium pump in the epithelial cells. The aim of the presented study was to assess the immediate and prolonged effect of nickel ions on the transport of sodium ions in tissues exposed to direct contact with nickel, including airways, digestive tract and the skin. The influence of 0.1 mM nickel solution was performed on the trachea (n = 34), intestine (n = 44), and skin (n = 51) samples descended from 16 New Zealand albino rabbits. The electrophysiological parameters were measured in a modified Ussing chamber in stationary conditions and during a 15-s mechanical-chemical stimulation. A statistically significant decrease in the electric resistance values and the smallest range of the measured potential were observed for the Ni-treated trachea specimens. The use of nickel solution did not affect the sodium transport in the intestine epithelium. The skin fragments showed altered sodium ion transport, as demonstrated by the lower range and intensity of the measured potential. The gastrointestinal tract seems to be an organ best adapted to contact with nickel ions. In airways, nickel ions most likely enter epithelial cells and the space between them, modifying proteins and the airway surface liquid. The skin turned out to be the most sensitive tissue to the intensification of sodium ion transport through nickel ions.

Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection.

Ferroptosis is a recently discovered form of programmed cell death. It is characterized by the accumulation of iron and lipid hydroperoxides in cells. Vitamin K is known to have antioxidant properties and plays a role in reducing oxidative stress, particularly in lipid cell membranes. Vitamin K reduces the level of reactive oxygen species by modulating the expression of antioxidant enzymes. Additionally, vitamin K decreases inflammation and potentially prevents ferroptosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) is associated with oxidant-antioxidant imbalance. Studies have shown that intensified ferroptosis occurs in various tissues and cells affected by COVID-19. Vitamin K supplementation during SARS-CoV-2 infection may have a positive effect on reducing the severity of the disease. Preliminary research suggests that vitamin K may reduce lipid peroxidation and inhibit ferroptosis, potentially contributing to its therapeutic effects in COVID-19 patients. The links between ferroptosis, vitamin K, and SARS-CoV-2 infection require further investigation, particularly in the context of developing potential treatment strategies for COVID-19.

The Role of Selected Trace Elements in Oxidoreductive Homeostasis in Patients with Thyroid Diseases.

Impaired levels of selenium (Se), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn) and iodine (I) in the organism may adversely affect the thyroid endocrine system. These trace elements play a role in the fight against oxidative stress as components of enzymes. Oxidative-antioxidant imbalance is considered a possible factor in many pathological conditions, including various thyroid diseases. In the available literature, there are few scientific studies showing a direct correlation of the effect of supplementation of trace elements on slowing down or preventing the occurrence of thyroid diseases in combination with the improvement of the antioxidant profile, or through the action of these elements as antioxidants. Among the available studies, it has been shown that an increase in lipid peroxidation levels and a decrease in the overall antioxidant defense status occur during such thyroid diseases as thyroid cancer, Hashimoto's thyroiditis and dysthyroidism. In studies in which trace elements were supplemented, the following were observed: a decrease in the level of malondialdehyde after supplementation with Zn during hypothyroidism and reduction in the malondialdehyde level after Se supplementation with a simultaneous increase in the total activity status and activity of antioxidant defense enzymes in the course of autoimmune thyroiditis. This systematic review aimed to present the current state of knowledge about the relationship between trace elements and thyroid diseases in terms of oxidoreductive homeostasis.

The Impact of Exercise on Redox Equilibrium in Cardiovascular Diseases.

Cardiovascular diseases constitute the most important public health problem in the world. They are characterized by inflammation and oxidative stress in the heart and blood. Physical activity is recognized as one of the best ways to prevent these diseases, and it has already been applied in treatment. Physical exercise, both aerobic and anaerobic and single and multiple, is linked to the oxidant-antioxidant imbalance; however, this leads to positive adaptive changes in, among others, the increase in antioxidant capacity. The goal of the paper was to discuss the issue of redox equilibrium in the human organism in the course of cardiovascular diseases to systemize updated knowledge in the context of exercise impacts on the organism. Antioxidant supplementation is also an important issue since antioxidant supplements still have great potential regarding their use as drugs in these diseases.

Characteristics of Selected Adipokines in Ascites and Blood of Ovarian Cancer Patients.

Ovarian cancer is one of the most common malignancies among women worldwide. The course of the disease is often latent and asymptomatic in the early stages, but as it develops, metastasis occurs, accompanied by accumulation of ascites in the peritoneal cavity. The ascites fluid constitutes a specific microenvironment influencing the processes of carcinogenesis. In ascites, signaling is mediated by various cytokines that control tumor cell proliferation, progression, metastasis, and chemoresistance. Adipokines, secreted into ascites and also appearing in blood, may be markers of ongoing processes related to the development of neoplastic disease. Moreover, a significant influence of adipocyte lipids on the growth of tumors, for which they are one of energy sources, is observed. Adiponectin, interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1), discussed in the present review, were found to mediate the effects of omentum metastasis through homing, migration and invasion of ovarian cancer cells. Further research on those adipokines seem to be a natural consequence, allowing for a better understanding of the mechanisms of neoplastic disease and determination of the treatment procedure.

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities.

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

Contribution of frequency bands to the loudness of broadband sounds: Tonal and noise stimuli.

Contributions of individual frequency bands to judgments of total loudness can be assessed by varying the level of each band independently from one presentation to the next and determining the relation between the change in level of each band and the loudness judgment. In a previous study, measures of perceptual weight obtained in this way for noise stimuli consisting of 15 bands showed greater weight associated with the highest and lowest bands than loudness models would predict. This was true even for noise with the long-term average speech spectrum, where the highest band contained little energy. One explanation is that listeners were basing decisions on some attribute other than loudness. The current study replicated earlier results for noise stimuli and included conditions using 15 tones located at the center frequencies of the noise bands. Although the two types of stimuli sound very different, the patterns of perceptual weight were nearly identical, suggesting that both sets of results are based on loudness judgments and that the edge bands play an important role in those judgments. The importance of the highest band was confirmed in a loudness-matching task involving all combinations of noise and tonal stimuli.

High frequency transient-evoked otoacoustic emission measurements using chirp and click stimuli.

Transient-evoked otoacoustic emissions (TEOAEs) at high frequencies are a non-invasive physiological test of basilar membrane mechanics at the basal end, and have clinical potential to detect risk of hearing loss related to outer-hair-cell dysfunction. Using stimuli with constant incident pressure across frequency, TEOAEs were measured in experiment 1 at low frequencies (0.7-8 kHz) and high frequencies (7.1-14.7 kHz) in adults with normal hearing up to 8 kHz and varying hearing levels from 9 to 16 kHz. In combination with click stimuli, chirp stimuli were used with slow, medium and fast sweep rates for which the local frequency increased or decreased with time. Chirp TEOAEs were transformed into equivalent click TEOAEs by inverse filtering out chirp stimulus phase, and analyzed similarly to click TEOAEs. To improve detection above 8 kHz, TEOAEs were measured in experiment 2 with higher-level stimuli and longer averaging times. These changes increased the TEOAE signal-to-noise ratio (SNR) by 10 dB. Slower sweep rates were investigated but the elicited TEOAEs were detected in fewer ears compared to faster rates. Data were acquired in adults and children (age 11-17 y), including children with cystic fibrosis (CF) treated with ototoxic antibiotics. Test-retest measurements revealed satisfactory repeatability of high-frequency TEOAE SNR (median of 1.3 dB) and coherence synchrony measure, despite small test-retest differences related to changes in forward and reverse transmission in the ear canal. The results suggest the potential use of such tests to screen for sensorineural hearing loss, including ototoxic loss. Experiment 2 was a feasibility study to explore TEOAE test parameters that might be used in a full-scale study to screen CF patients for risk of ototoxic hearing loss.

Current Research on the Safety of Pyrethroids Used as Insecticides.

Pyrethroids are synthetic derivatives of natural pyrethrins extracted from Chrysanthemum cinerariaefolium. They are 2250 times more toxic to insects than to vertebrates due to insects' smaller size, lower body temperature and more sensitive sodium channels. In particular, three pyrethroid compounds, namely deltamethrin, permethrin, and alpha-cypermethrin, are commonly used as insecticides and are recommended for in-home insect control because they are considered to be relatively non-toxic to humans in all stages of life. However, recent data show that they are not completely harmless to human health as they may enter the body through skin contact, by inhalation and food or water, and absorption level depending on the type of food. Permethrin seems to have an adverse effect on fertility, the immune system, cardiovascular and hepatic metabolism as well as enzymatic activity. Deltamethrin induces inflammation, nephro- and hepatotoxicity and influences the activity of antioxidant enzymes in tissues. Alpha-cypermethrin may impair immunity and act to increase glucose and lipid levels in blood. The aim of the review is to provide comprehensive information on potential hazards associated to human exposure to deltamethrin, permethrin and alpha-cypermethrin. The results of presented studies prove that the insecticides must be used with great caution.

Relative contributions of specific frequency bands to the loudness of broadband sounds.

Listeners with normal hearing (NH) and sensorineural hearing loss (SNHL) were asked to compare pairs of noise stimuli and choose the louder noise in each pair. Each noise was made up of 15, two-ERBN (equivalent rectangular bandwidth) wide frequency bands that varied independently over a 12-dB range from one presentation to the next. Mean levels of the bands followed the long-term average speech spectrum (LTASS) or were set to 43, 51, or 59 dB sound pressure level (SPL). The relative contribution of each band to the total loudness of the noise was determined by computing the correlation between the difference in levels for a given band on every trial and the listener's decision on that trial. Weights for SNHL listeners were governed by audibility and the spectrum of the noise stimuli, with bands near the spectral peak of the LTASS noise receiving greatest weight. NH listeners assigned greater weight to the lowest and highest bands, an effect that increased with overall level, but did not assign greater weight to bands near the LTASS peak. Additional loudness-matching and paired-comparison studies using stimuli missing one of the 15 bands showed a significant contribution by the highest band, but properties other than loudness may have contributed to the decisions.

[The application of N-acetylcysteine in optimization of specific pharmacological therapies]. / Zastosowanie N-acetylocysteiny do optymalizacji specyficznych terapii farmakologicznych.

Based on the analysis of data from clinical trials it could be postulated that N-acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L-cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight. Side effects are relatively rare. NAC is used as an mucolytic agent in adjunctive therapy of respiratory diseases causing the retention of secretions, as well as an antidote in the treatment of paracetamol poisoning. Moreover, NAC protects against the toxic effects of reactive oxygen species and their active metabolites. NAC is involved in free radical scavenging processes via several independent mechanisms, including a direct reduction of free radicals, providing substrates for oxidation-reduction reactions and activation of antioxidant enzymes. In the blood, NAC decreases the level of low density lipoprotein peroxidation. In various tissues, NAC may increase the levels of glutathione and cysteine and stimulate the superoxide dismutase action. NAC is used as a supplement in the treatment of various diseases associated with impaired exterior and intracellular oxidative balance. NAC increases the concentrations of amino acids and their derivatives, including cysteine, cystine, and glutathione. It also stabilizes the antioxidant status of the cells and the intercellular spaces. NAC changes the levels of transcription factors, modifying the transcription of selected genes and acting on the protein translation. It works on the activation of several enzymes in the cells and outside the cells. Based on the analysis of data from clinical trials it can be concluded, that an administration of NAC may be beneficial for these groups of patients, in whom the reversible accumulation and the negative action of free radicals was observed.

Deriving loudness growth functions from categorical loudness scaling data.

The goal of this study was to reconcile the differences between measures of loudness obtained with continuous, unbounded scaling procedures, such as magnitude estimation and production, and those obtained using a limited number of discrete categories, such as categorical loudness scaling (CLS). The former procedures yield data with ratio properties, but some listeners find it difficult to generate numbers proportional to loudness and the numbers cannot be compared across listeners to explore individual differences. CLS, where listeners rate loudness on a verbal scale, is an easier task, but the numerical values or categorical units (CUs) assigned to the points on the scale are not proportional to loudness. Sufficient CLS data are now available to assign values in sones, a scale proportional to loudness, to the loudness categories. As a demonstration of this approach, data from Heeren, Hohmann, Appell, and Verhey [J. Acoust. Soc. Am. 133, EL314-EL319 (2013)] were used to develop a CUsone metric, whose values were then substituted for the original CU values in reanalysis of a large set of CLS data obtained by Rasetshwane, Trevino, Gombert, Liebig-Trehearn, Kopun, Jesteadt, Neely, and Gorga [J. Acoust. Soc. Am. 137, 1899-1913 (2015)]. The resulting data are well fitted by power functions and are in general agreement with previously published results obtained with magnitude estimation, magnitude production, and cross modality matching.

Effects of relative and absolute frequency in the spectral weighting of loudness.

The loudness of broadband sound is often modeled as a linear sum of specific loudness across frequency bands. In contrast, recent studies using molecular psychophysical methods suggest that low and high frequency components contribute more to the overall loudness than mid frequencies. In a series of experiments, the contribution of individual components to the overall loudness of a tone complex was assessed using the molecular psychophysical method as well as a loudness matching task. The stimuli were two spectrally overlapping ten-tone complexes with two equivalent rectangular bandwidth spacing between the tones, making it possible to separate effects of relative and absolute frequency. The lowest frequency components of the "low-frequency" and the "high-frequency" complexes were 208 and 808 Hz, respectively. Perceptual-weights data showed emphasis on lowest and highest frequencies of both the complexes, suggesting spectral-edge related effects. Loudness matching data in the same listeners confirmed the greater contribution of low and high frequency components to the overall loudness of the ten-tone complexes. Masked detection thresholds of the individual components within the tone complex were not correlated with perceptual weights. The results show that perceptual weights provide reliable behavioral correlates of relative contributions of the individual frequency components to overall loudness of broadband sounds.

2-Allylaminothiazole and 2-allylaminodihydrothiazole derivatives: synthesis, characterization, and evaluation of bioactivity.

ABSTRACT: Some reactions of selected chlorooxoesters and haloesters with a 1-allylthiourea under various conditions have been performed. The reactions have been performed in methanol in alkaline and neutral environment. Condensation of 1-allylthiourea with chlorooxoesters has been further led via acetal as intermediate compound. As a result, the compounds containing thiazole and a 4,5-dihydrothiazole ring with a good yield have been obtained. The structures of the compounds were verified by 1H NMR, 13C NMR as well as X-ray diffraction analysis. Due to the potential biological activity of the synthesized compounds, the parameters of their bioavailability have been determined, and the probability of pharmacological action has been defined. All of the obtained compounds fulfilled the rule of five, which indicate their good absorption after oral intake. The probability of pharmacological action and potential targets calculated for the obtained compounds show that they can be potential drugs.

Effects of reverberation on speech recognition in stationary and modulated noise by school-aged children and young adults.

OBJECTIVES: The purpose of this study was to determine how combinations of reverberation and noise, typical of environments in many elementary school classrooms, affect normal-hearing school-aged children's speech recognition in stationary and amplitude-modulated noise, and to compare their performance with that of normal-hearing young adults. In addition, the magnitude of release from masking in the modulated noise relative to that in stationary noise was compared across age groups in nonreverberant and reverberant listening conditions. Last, for all noise and reverberation combinations the degree of change in predicted performance at 70% correct was obtained for all age groups using a best-fit cubic polynomial. DESIGN: Bamford-Kowal-Bench sentences and noise were convolved with binaural room impulse responses representing nonreverberant and reverberant environments to create test materials representative of both audiology clinics and school classroom environments. Speech recognition of 48 school-aged children and 12 adults was measured in speech-shaped and amplitude-modulated speech-shaped noise, in the following three virtual listening environments: nonreverberant, reverberant at 2 m, and reverberant at 6 m. RESULTS: Speech recognition decreased in the reverberant conditions and with decreasing age. Release from masking in modulated noise relative to stationary noise decreased with age and was reduced by reverberation. In the nonreverberant condition, participants showed similar amounts of masking release across ages. The slopes of performance-intensity functions increased with age, with the exception of the nonreverberant modulated masker condition. The slopes were steeper in the stationary masker conditions, where they also decreased with reverberation and distance. In the presence of a modulated masker, the slopes did not differ between the two reverberant conditions. CONCLUSIONS: The results of this study reveal systematic developmental changes in speech recognition in noisy and reverberant environments for elementary-school-aged children. The overall pattern suggests that younger children require better acoustic conditions to achieve sentence recognition equivalent to their older peers and adults. In addition, this is the first study to report a reduction of masking release in children as a result of reverberation. Results support the importance of minimizing noise and reverberation in classrooms, and highlight the need to incorporate noise and reverberation into audiological speech-recognition testing to improve predictions of performance in the real world.

Measuring speech recognition in children with cochlear implants in a virtual classroom.

PURPOSE: To determine the feasibility of using a virtual auditory test material to evaluate reverberation and noise effects on speech recognition of pediatric cochlear implant (CI) users and to compare their performance with that of children with normal hearing. METHOD: Virtual test materials representing nonreverberant and reverberant environments were used to measure speech recognition of 7 children with CIs in quiet and in noise, and of 18 children with normal hearing in the quiet condition. Performance of CI users in noise (signal-to-noise ratio resulting in 50% performance) was compared to normative data from a previous study (Neuman, Wroblewski, Hajicek, & Rubinstein, 2010). For CI users, stimuli were sent directly to the CI speech processor via auxiliary input, whereas children with normal hearing were tested using insert phones. RESULTS: The speech recognition of children with CIs decreased significantly in the reverberant condition. There were individual differences in susceptibility to reverberation. Children with CIs also required higher signal-to-noise ratios than children with normal hearing in the reverberant condition. CONCLUSION: Direct connect testing with reverberant test materials allows assessment of speech recognition under conditions typical of classrooms and could be useful in identifying children with CIs whose performance decreases significantly in the presence of reverberation and noise.

[The evaluation of amylolytic activity of strains of coagulase negative staphylococci]. / Ocena amylolitycznej aktywnosci szczepów gronkowców koagulazo-ujemnych.

Amylase activity of 30 strains of Staphylococcus spp. was determined by Tryptic Soy Agar on supplemented with 1.0% starch as the substrate. After incubation (time incubation 24 h or 168 h), the plates were flooded with Lugol solution. A clear zone around the colonies indicated amylase activity. The 23 (76.7%) strains CNS demonstrated the amylase activity. It was observed that 17 (80.9%) strains of S. epidermidis, and 6 (66.7%) strains non-S. epidermidis, starch hydrolyzed. Amylase production depends of time incubation (frequently 168 h) and growth atmosphere (frequently oxygen atmosphere)

A meta-analysis of outcomes of hydration intervention on phonation threshold pressure.

OBJECTIVES: Vocal fold hydration is purported to promote optimal biomechanical characteristics of vocal fold mucosa, increase efficiency of vocal fold oscillation, and enhance voice quality. The purpose of this work was to determine the magnitude and consistency of the effect of vocal fold hydration on vocal fold function across published clinical studies. METHODS: We completed a comprehensive meta-analysis of the effects of superficial and systemic vocal fold hydration on phonation threshold pressure (PTP), a measure of efficiency of voice production. RESULTS: We identified 34 studies that examined the effects of hydration on vocal function. Of these studies, 14 examined the effects of hydration on PTP. Nine of these articles met the criteria for inclusion in this analysis. We observed an average effect size of 0.33, indicating that, overall, hydration treatment demonstrated a tendency to reduce PTP. However, this decrease in phonatory effort did not reach significance at the 95% confidence level. The effects of hydration intervention varied considerably across studies (-0.19 to 3.96). We considered that two factors, pitch level of the task and vocal health of participants, may have contributed to this variability in findings. However, our analysis found that these factors could not account for differences in effect size. CONCLUSION: To understand the variability in outcomes across studies, the role of factors that may impact the effects of hydration, such as the amount, type, and duration of intervention, must be determined. Only then can we obtain data to guide best clinical practice for protecting and rehabilitating vocal function.