The antiglycation potential of H1 receptor antagonists - in vitro studies in bovine serum albumin model and in silico molecular docking analyses.

The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.

Antioxidant and Anti-Glycation Potential of H2 Receptor Antagonists-In Vitro Studies and a Systematic Literature Review.

Background: Histamine H2 receptor antagonists are a group of drugs that inhibit gastric juice secretion in gastrointestinal diseases. However, there is evidence to suggest that H2 blockers have a broader spectrum of activity. The antioxidant properties of H2 blockers have not been fully elucidated, and their anti-glycation potential has not been studied to date. Therefore, this is the first study to compare the antioxidant and antiglycation potentials of the most popular H2 antagonists (ranitidine, cimetidine, and famotidine) on protein glycoxidation in vitro. Methods: Bovine serum albumin (BSA) was glycated using sugars (glucose, fructose, galactose, and ribose) as well as aldehydes (glyoxal and methylglyoxal). Results: In the analyzed group of drugs, ranitidine was the only H2 blocker that significantly inhibited BSA glycation in all tested models. The contents of protein carbonyls, protein glycoxidation products (↓dityrosine, ↓N-formylkynurenine), and early (↓Amadori products) and late-stage (↓AGEs) protein glycation products decreased in samples of glycated BSA with the addition of ranitidine relative to BSA with the addition of the glycating agents. The anti-glycation potential of ranitidine was comparable to those of aminoguanidine and Trolox. In the molecular docking analysis, ranitidine was characterized by the lowest binding energy for BSA sites and could compete with protein amino groups for the addition of carbonyl groups. H2 blockers also scavenge free radicals. The strongest antioxidant properties are found in ranitidine, which additionally has the ability to bind transition metal ions. The systematic literature review also revealed that the anti-glycation effects of ranitidine could be attributed to its antioxidant properties. Conclusions: Ranitidine showed anti-glycation and antioxidant properties. Further research is needed, particularly in patients with diseases that promote protein glycation.

The effect of the third dose of the BNT162b2 vaccine on anti-SARS-CoV-2 spike antibody levels in healthcare workers with and without COVID-19 infection.

AIM: A third (booster) dose of the anti-SARS-CoV-2 vaccine became necessary due to the observed decrease in anti-SARS-CoV-2S antibody levels over time, new mutations, and low global vaccination rates. In this study, anti-SARS-CoV-2S antibody levels were measured (ECLIA assay) in 50 healthcare workers with and without a history of COVID-19 infection to determine the humoral immune response to the third dose of the BNT162b2 vaccine. METHODS: Antibody levels were determined in the blood serum, and blood was sampled for analysis 20-40 days after the administration of the booster dose. RESULTS: A greater increase in anti-SARS-CoV-2S antibody titers was noted in persons without a history of infection, but antibody levels continued to be higher in previously infected individuals when the results were adjusted for age, gender, BMI, type of work, and presence of comorbidities. CONCLUSION: The results of this study can be used to improve the vaccination strategy for the general population.KEY MESSAGESThree doses of the vaccine BNT162b2 strongly stimulate the immune system to produce anti-SARS-CoV-2s antibodies, especially in people with a previous infection COVID-19.Age, gender, and BMI may be associated with different humoral immune response to the BNT162b2 vaccine.

An Assessment of the Serum Activity of ADH and ALDH in Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC; previously known as primary biliary cirrhosis) is a chronic inflammation-induced cholestatic process in the liver. Antimitochondrial antibodies (AMAs) are observed in around 90% of patients, which suggests that PBC is an autoimmune disease. Alcohol dehydrogenase (ADH), ADH isoenzymes and aldehyde dehydrogenase (ALDH) are localized in the liver, and they are useful markers of liver dysfunction. In this study, the activity of total ADH, ADH isoenzymes and ALDH was evaluated in the blood serum of patients with PBC. The experimental group comprised 50 PBC patients, both male and female, aged 28-67. The control group consisted of 50 healthy subjects, both male and female, aged 25-65. The serum activity of class I ADH, class II ADH and ALDH was measured by spectrofluorophotometry, whereas total ADH and class III ADH activity was determined by photometry methods. The activity of class I ADH and total ADH was significantly higher in the experimental group than in the control group (p < 0.001). An increase in class I ADH and total ADH activity indicates that the isoenzyme class I ADH is released by compromised liver cells and can be useful diagnostic markers of PBC.

Salivary Xanthine Oxidase as a Potential Biomarker in Stroke Diagnostics.

Stroke is one of the most common cerebrovascular diseases. Despite significant progress in understanding stroke pathogenesis, cases are still increasing. Thus, laboratory biomarkers of stroke are sought to allow rapid and non-invasive diagnostics. Ischemia-reperfusion injury is an inflammatory process with characteristic cellular changes leading to microvascular disruption. Several studies have shown that hyperactivation of xanthine oxidase (XO) is a major pathogenic factor contributing to brain dysfunction. Given the critical role of XO in stroke complications, this study aimed to evaluate the activity of the enzyme and its metabolic products in the saliva of stroke subjects. Thirty patients in the subacute phase of stroke were included in the study: 15 with hemorrhagic stroke and 15 with ischemic stroke. The control group consisted of 30 healthy subjects similar to the cerebral stroke patients regarding age, gender, and status of the periodontium, dentition, and oral hygiene. The number of individuals was determined a priori based on our previous experiment (power of the test = 0.8; α = 0.05). The study material was mixed non-stimulated whole saliva (NWS) and stimulated saliva (SWS). We showed that activity, specific activity, and XO output were significantly higher in NWS of ischemic stroke patients than in hemorrhagic stroke and healthy controls. Hydrogen peroxide and uric acid levels were also considerably higher in NWS of ischemic stroke patients. Using receiver operating curve (ROC) analysis, we demonstrated that XO-specific activity in NWS distinguishes ischemic stroke from hemorrhagic stroke (AUC: 0.764) and controls (AUC: 0.973) with very high sensitivity and specificity. Saliva collection is stress-free, requires no specialized medical personnel, and allows continuous monitoring of the patient's condition through non-invasive sampling multiple times per day. Salivary XO also differentiates with high accuracy (100%) and specificity (93.75%) between stroke patients with mild to moderate cognitive decline (AUC = 0.988). Thus, salivary XO assessment may be a potential screening tool for a comprehensive neuropsychological evaluation. To summarize, our study demonstrates the potential utility of salivary XO in the differential diagnosis of stroke.

Anti-SARS-CoV-2S Antibody Levels in Healthcare Workers 10 Months after the Administration of Two BNT162b2 Vaccine Doses in View of Demographic Characteristic and Previous COVID-19 Infection.

Antibody levels that confer full protection against SARS-CoV-2 infection after the administration of different vaccine brands as well as the factors influencing the humoral immune response have been analyzed extensively ever since the vaccination program was launched in late 2020. The aim of this study was to determine anti-SARS-CoV-2S antibody titers in 100 healthcare workers 10 months after the administration of two BNT162b2 vaccine doses, and to investigate the influence of demographic characteristics, the presence of comorbidities and history of COVID-19 infection. The results were compared with antibody levels that were determined eight months after the administration of two BNT162b2 vaccine doses in our previous study. Antibody levels in venous blood serum were measured by the ECLIA method with the use of the Roche Cobas e411 analyzer. In all tested subjects, antibody titers remained high 10 months after vaccination, particularly in recovered COVID-19 patients, and only a minor decrease was observed relative to the values noted two months earlier.

The Influence of Two Priming Doses of Different Anti-COVID-19 Vaccines on the Production of Anti-SARS-CoV-2 Antibodies After the Administration of the Pfizer/BioNTech Booster.

Introduction: A global vaccination program was implemented in late 2020 to end the pandemic caused by the SARS-CoV-2 virus. However, the immune response elicited by the vaccines proved to be insufficient due to the rapid emergence of new viral mutations. Therefore, the factors influencing cellular and humoral immune responses after the administration of different vaccines against SARS-CoV2 need to be identified. Materials: In the present study, anti-SARS-CoV-2 antibody titers were analyzed 20 to 50 days after the administration of a third (booster) dose of the BNT162b2 vaccine in 192 residents of the city of Olsztyn (Poland) primed with two AstraZeneca or Pfizer/BioNTech vaccines. Methods: Antibody titers were determined in venous blood serum in the ECLIA test using the Cobas e411 Roche analyzer. Results: The study revealed that persons who received three doses of the Pfizer/BioNTech vaccine had significantly higher antibody titers than those who received two doses of AstraZeneca and a booster dose of Pfizer/BioNTech.

Activity of Total Alcohol Dehydrogenase, Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in the Serum of Patients with Alcoholic Fatty Liver Disease.

Background and objectives: The aim of the current study was to assess the use of determinations of total alcohol dehydrogenase and the activity of its isoenzymes as well as aldehyde dehydrogenase in the serum of patients with alcohol liver disease. Materials and Methods: The testing was performed on the serum of 38 patients with alcoholic fatty liver (26 males and 12 females aged 31-75). The total activity of ADH was determined by the colorimetric method. The activity of ADH I and ADH II, as well as ALDH, was determined by the spectrofluorometric method using fluorogenic specific substrates. The activity of isoenzymes of other classes was determined by spectrophotometric methods using substrates. Results: A statistically significantly higher ADH I activity was noted in the serum of patients with alcoholic fatty liver (4.45 mIU/L) compared to the control group (2.04 mIU/L). A statistically significant increase in the activity was also noted for the class II alcohol dehydrogenase isoenzyme (29.21 mIU/L, control group: 15.56 mIU/L) and the total ADH (1.41 IU/L, control group: 0.63 IU/L). Conclusions: The obtained results imply the diagnostic usefulness of the determination of AHD total, ADH I, and ADH II activity in the serum of patients with alcoholic fatty liver.