Hair Mercury Levels in Pregnant Women: Fish Consumption as a Determinant of Exposure.

The consumption of fish in food may contain mercury, a harmful element and dangerous chemical detrimental to human health. The purpose of this study was to determine the mercury level in the hair of pregnant women with different fish intakes in their diets. The concentration of total mercury in hair was determined using an atomic absorption spectrometer. In this study, 98 pregnant women were invited to participate (aged from 18 to 48 years). The mean content of mercury in the hair of pregnant women in Northwestern Russia was 0.428 mg/kg (ranging from 0.018 to 3.1 mg/kg). As a result, 22% of women had mercury values above 0.58 mg/kg, which is considered dangerous for the fetus. The hair mercury concentration in a village area was higher than that in a city area (i.e., 0.548 mg/kg and 0.326 mg/kg). Moreover, the maximum level of mercury was noted for a group of pregnant women who consumed more than 5 kg/month of fish and fish products. Furthermore, the consumption of freshwater fish in the diet leads to a higher mercury content in the hair of pregnant women than the consumption of marine fish.

The Impact of Social Well-Being on Population Diet Nutritional Value and Antiradical Status.

The paper presents the result of assessing the antiradical status of consumers (in the context of Russia) in connection with their well-being. This approach is based on a multistage study, in which the results of sociological surveys were applied, as well as estimates of the antiradical potential (ARP) of diets obtained using neural networks, bootstrapping the chemical composition of diets, and calculating reference values using mathematical models. The paper presents data collected from residents living in the territories of at least 21 regions and cities of Russia: Magadan, Saint Petersburg, Moscow, Krasnodar, Lipetsk, Vladivostok, Novosibirsk, Omsk, Voronezh, etc. A total of 1001 people were interviewed, which, according to our calculations, gives a margin of error in value of approximately 3.1%. To calculate the lack of vitamins in the diets of residents of the Russian Federation, data on the chemical composition of food products from the FNDDS database were used. The assessment of dietary habits showed a lack of vitamins below the recommended level in 73% of Russians for vitamin D, 59% for retinol, 38% for ß-carotenes, 13% for vitamin E, and 6% for ascorbic acid. The study showed that at least 36% of the Russian population has a low antiradical status, while it was found that "poor" consumers are more likely to consume economically more expensive foods (in terms of their nutritional value). The "poor" segments of the population consume 180-305% more canned food and 38-68% more sweet carbonated drinks than other social groups, but their consumption of vegetables is 23-48% lower. On the contrary, "wealthy" consumers consume 17-25% more complex (varied) dishes, 10-68% more fresh vegetables, and 8-39% more fish. From the obtained values it follows that consumers with low levels of ARP in their diets are in a group with an increased probability of a number of "excess" diseases (diseases of the cardiovascular system, obesity, etc.). In general, the ARP values of food consumed for low-income segments of the population were 2.3 times lower (the ratio was calculated as the percentage of consumers below the level of 11,067 equivalents necessary for the disposal of free radicals generated in the human body per day) than for those who can afford expensive food (consumers with high income). A simple increase in consumption of unbalanced foods, in our opinion, will only contribute to the entry of these consumers into the "average diet trap". All this makes it imperative to develop comprehensive measures to create a new concept of public catering; otherwise, we can expect a reduction in both the health of the population and the performance of the economy of the whole country.

Estimating the Mass of Food Components Necessary for the Utilization of Free Radical Particles in the Human Body.

The article proposes an algorithm for an approximate assessment of the molar volume of free radicals generated in the human body per day. It takes into account the act of breathing, physical activity, food consumption, the influence of unfavorable environmental conditions, exposure to xenobiotics, as well as bad habits (alcohol and tobacco smoking). A calculation of the required set of the most commonly used food products for the disposal of free radicals was made. The calculation is a structure of four blocks with the possibility of adding optional data from human population genetic studies, environmental conditions, etc. In the proposed algorithm, the results of antiradical activity (ARA) of food products are used as input, including the results of predicting antiradical activity using artificial neural networks (ANN), which we published earlier. Based on the accepted values of one equivalent (in terms of the activity of 1 µmol of ascorbic acid), it was shown (for our data) that for the utilization of all free radicals produced in the human body per day, it will take an average of ≈260 to ≈540 g of food components in terms of dry mass (including proteins, fats, carbohydrates, etc.). At the same time, for the utilization of consumed xenobiotics, from 220 mg (in terms of vitamin C) to 260 mg (in terms of acetylcysteine -NAC) of additional plastic components or 11.5-13.0 g of essential amino acids will be required, which must be taken into account when calculating diets. This approach will be useful in the development of new functional foods, as well as in assessing the possible impact of diets on human health. Another applied point of this study is related to the possibility of using these data for better detailing and selection of food products for people working in conditions of increased radiation (in space conditions), in contact with harmful substances (chemical synthesis and production), for people practicing increased physical activity (bodybuilding and sports), and for the purposes of medical nutritional therapy.

Antiradical Potential of Food Products as a Comprehensive Measure of Their Quality.

Antiradical potential (ARP) is an important measure of food safety. In addition, it directly or indirectly affects the rate of occurrence of a number of human pathologies. Using a photocolorimetric analysis of DPPH (2,2-diphenyl-1-picrylhydrazyl) solutions, we estimated the antiradical potential of food raw materials, food concentrates, biologically active substances, and wild plants. We conducted approximately 1500 analyses of almost 100 food products selected from 11 food groups: vegetables, milk, meat, fish, cereals and bread, drinks (including tea and coffee), etc. With a confidence interval (CI) of 95%, the average values for animal products range from 15.87 to 18.70 ascorbic acid equivalents per gram of dry matter. For plant materials, the range is 474.54-501.50 equivalents when wild herbs are included and 385.02-408.83 equivalents without taking herbs into account. The antiradical potential of the biologically active substances we studied ranged from 706.84 to 847.77 equivalents per gram of dry matter, which makes it possible to use some of the components to repair products with low ARP values, for example, bread and baked goods, confectionery, milk and dairy products, carbonated drinks, and juice. In this study, a low ARP value is associated with a reduction in the shelf life of products and a deterioration in their organoleptic properties; therefore, we propose using ARP as an important reference for describing the quality of food products and raw food materials.

Research into Morphofunctional Characteristics of Erythrocytes in COVID-19 Patients.

In this paper, the erythrocytes of healthy donors and people with a confirmed diagnosis of COVID-19 were tested by Raman spectroscopy and laser interference microscopy. We argue that erythrocytes (red blood cells) in COVID-19 patients have an irregular shape, and their morphometric characteristics are impaired in comparison to healthy red blood cells. Raman spectroscopy also allows us to detect a decreased oxygen transport function of these erythrocytes. The combination of these methods-Raman spectroscopy and laser interference microscopy-is a highly effective method for the diagnosis of SARS-CoV-2.

The origin of the hysteresis in cyclic voltammetric response of alkaline methanol electrooxidation.

The mechanism of the alkaline methanol electrooxidation reaction on platinum is complex and not fully understood. However, a better understanding will facilitate reaching the theoretical performance of an alkaline methanol fuel cell. Cyclic voltammetry is an often used method to investigate the mechanism of electrochemical reactions. The cyclic voltammogram of methanol electrooxidation shows a hysteresis in potential between the oxidation peaks in the forward and backward scans. The origin of this hysteresis has not been fully clarified. By means of parameter variations, such as the upper potential or the starting point of the CV measurements, and by physicochemical modeling, we investigate the formation of platinum oxides as a possible cause of this behaviour. The experiments show that the formation of platinum oxides is more likely to cause the hysteresis than the strongly adsorbed intermediates, which are formed during the forward scan. The simulation includes the formation of platinum oxide species and supports the experimental results that the hysteresis is due to the formation and reduction of platinum oxides. Besides, the simulation reveals that in the investigated potential area, different oxide forms are present.

ST-elevation myocardial infarction, pulmonary embolism, and cerebral ischemic stroke in a patient with critically low levels of natural anticoagulants.

This clinical case report describes the simultaneous development of an acute myocardial infarction, stroke, and a massive pulmonary thromboembolism in a 44-year-old patient - a carrier of the thrombophilia gene polymorphisms: MTHFR C677T, А1298C, PAI-1 4G/5G, ITGA2 C807T. Multifocal thrombosis was probably due to the initial congenital deficiency of anticoagulants, accompanied by a decrease in antithrombin III and protein C, against the background of their critical consumption in cascade thrombosis, in combination with the carrier of polymorphisms of moderate and low thrombogenic risk. This case is unique in that there is usually a tendency toward clinical thrombosis when the level of antithrombin III is less than 70%. Such patients develop thrombosis at a younger age, and by the age of 35-40 years usually have a verified diagnosis of extremely high-risk hereditary thrombophilia. In this case, multifocal thrombosis was accompanied by critically low values of anticoagulants: antithrombin III - 3.4%, and protein C - 36.8%. The patient had suffered from epilepsy since childhood and took anticonvulsant drugs that increase the deficit of active folic acid and can lead to hyperhomocysteinemia, which in this case, against the background of an innate decrease in the activity of methyltetrahydrofolate reductase, could have aggravated the situation. .

Simeprevir with peginterferon α-2a/ribavirin for chronic hepatitis C virus genotype 1 infection in treatment-experienced patients: an open-label, rollover study.

BACKGROUND: This Phase 3, open-label, rollover study (NCT01323244) investigated the efficacy and safety of simeprevir plus peginterferon α-2a (PegIFNα-2a) and ribavirin (RBV) in a well-characterized population of HCV genotype 1 (GT1)-infected treatment-experienced patients. METHODS: Patients who had failed PegIFNα/RBV treatment in the placebo arm of a previous Phase 2/3 simeprevir study (Phase 2/3 group, n = 125), or had been exposed to HCV direct-acting antivirals (simeprevir or other) for up to 14 days in a selected Phase 1 study (Phase 1 group, n = 16), were eligible. Phase 2/3 group patients were classified according to prior relapse, breakthrough, or non-response (null response, partial response, non-classifiable non-response) to PegIFNα/RBV. Eight patients in the Phase 1 group received short-term (≤14 days) simeprevir. Treatment comprised simeprevir 150 mg once daily (QD) plus PegIFNα-2a/RBV for 12 weeks followed by PegIFNα-2a/RBV for 12 or 36 weeks (using response-guided therapy [RGT] to determine total treatment duration in Phase 2/3 prior relapsers or breakthrough) or 36 weeks fixed (Phase 2/3 group non-responders and Phase 1 group). The primary endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). RESULTS: Phase 2/3 group: SVR12 rate was 69.6% (87/125) overall; 92.7% (51/55), 60.0% (6/10), 64.3% (18/28), and 36.7% (11/30) in patients with prior relapse, viral breakthrough, partial response, or null response, respectively. SVR12 rates were similar for patients with HCV GT1a (66.0% [33/50]) and GT1b infection (72.0% [54/75]) and among HCV GT1a-infected patients with/without a baseline Q80K polymorphism (66.7% [8/12] and 65.8% [25/38], respectively). The majority of RGT-eligible patients (prior viral relapse or breakthrough) met RGT criteria (89.2% [58/65]); of these, 89.7% (52/58) achieved SVR12. Overall, 16.0% (20/125) of patients experienced on-treatment failure and 14.4% (18/125) experienced post-treatment failure (15 relapses, 3 missing data). Phase 1 group (simeprevir-naïve and -experienced patients combined): SVR12 rate was 37.5% (6/16). Safety and tolerability findings were comparable to those of the feeder studies. CONCLUSIONS: The majority of RGT-eligible patients met criteria for shortening treatment to 24 weeks in total. Simeprevir 150 mg QD with PegIFNα-2a/RBV led to a high SVR rate among prior relapsers with HCV GT1 infection. No new safety signals were noted. TRIAL REGISTRATION: NCT01323244 . (date of registration: March 24, 2011).

A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.

BACKGROUND: A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. METHODS: Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. RESULTS: A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. CONCLUSIONS: In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.

Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia.

AIM: To evaluate addition of boceprevir to peginterferon/ribavirin (PR) in Russian patients with chronic hepatitis C virus (HCV). METHODS: Treatment-naive (TN) and treatment-experienced (TE) patients (who had failed prior treatment with PR for ≥ 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebo-controlled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. TN patients randomized to triple therapy received boceprevir (800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8 (TW8) HCV RNA levels. TE patients received boceprevir plus PR for 32 wk and then further therapy according to TW8 HCV RNA levels. Treatment was discontinued for TN patients with detectable HCV RNA at TW24 and TE patients with detectable HCV RNA at TW12 because of futility. The primary efficacy end point was sustained virologic response (SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy. RESULTS: SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2% (95%CI: 16.4-41.5; P < 0.0001). Rates of SVR were higher in the boceprevir arm in both TN and TE patient groups (TN 78.4% vs 56.3%; TE 69.4% vs 30.0%). Within TE patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type (null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both TN (86%) and TE (71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone (47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia (< 10 g/dL) and those without anemia (71.2% vs 77.4%). CONCLUSION: Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.

Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial.

BACKGROUND & AIMS: Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV. METHODS: We analyzed data from patients who did not respond (null response), had a partial response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66). All patients were followed for 24 weeks after planned end of treatment; the primary end point was the proportion of patients with sustained virologic response (SVR; undetectable HCV RNA) at that time point. RESULTS: Overall, rates of SVR at 24 weeks were significantly higher in the groups given simeprevir than those given placebo (61%-80% vs 23%; P < .001), regardless of prior response to PegIFN and RBV (simeprevir vs placebo: prior null response, 38%-59% vs 19%; prior partial response, 48%-86% vs 9%; prior relapse, 77%-89% vs 37%). All groups had comparable numbers of adverse events; these led to discontinuation of simeprevir or placebo and/or PegIFN and RBV in 8.8% of patients given simeprevir and 4.5% of those given placebo. CONCLUSIONS: In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR at 24 weeks compared with patients given placebo, PegIFN, and RBV and was generally well tolerated. ClinicalTrials.gov number: NCT00980330.

Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: the randomized PILLAR study.

UNLABELLED: The phase IIb, double-blind, placebo-controlled PILLAR trial investigated the efficacy and safety of two different simeprevir (SMV) doses administered once-daily (QD) with pegylated interferon (Peg-IFN)-α-2a and ribavirin (RBV) in treatment-naïve patients with HCV genotype 1 infection. Patients were randomized to one of five treatments: SMV (75 or 150 mg QD) for 12 or 24 weeks or placebo, plus Peg-IFN and RBV. Patients in the SMV arms stopped all treatment at week 24 if response-guided therapy (RGT) criteria were met; patients not meeting RGT continued with Peg-IFN and RBV until week 48, as did patients in the placebo control group. Sustained virologic response (SVR) rates measured 24 weeks after the planned end of treatment (SVR24) were 74.7%-86.1% in the SMV groups versus 64.9% in the control group (P < 0.05 for all comparisons [SMV versus placebo], except SMV 75 mg for 24 weeks). Rapid virologic response (HCV RNA <25 IU/mL undetectable at week 4) was achieved by 68.0%-75.6% of SMV-treated and 5.2% of placebo control patients. According to RGT criteria, 79.2%-86.1% of SMV-treated patients completed treatment by week 24; 85.2%-95.6% of these subsequently achieved SVR24. The adverse event profile was generally similar across the SMV and placebo control groups, with the exception of mild reversible hyperbilirubinemia, without serum aminotransferase abnormalities, associated with higher doses of SMV. CONCLUSION: SMV QD in combination with Peg-IFN and RBV significantly improves SVR rates, compared with Peg-IFN and RBV alone, and allows the majority of patients to shorten their therapy duration to 24 weeks.

Clinical management of drug-drug interactions in HCV therapy: challenges and solutions.

Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted drug-drug interaction studies and a list of contraindicated medications is not enough for the clinical management of these drug-drug interactions. Knowledge of pharmacokinetic profiles and concentration-effect relationships is key for the interpretation of these data, and insight into how to manage these interactions (e.g., dose adjustments, safe alternatives and therapeutic drug monitoring) is of equal importance. This review provides a practical overview of the safe and effective management of these clinical challenges.