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In this study, the fungus strain LS-4.2 isolated from the bottom sediments of Lake Lower Suzdalskoe was tested for its algicidal activity. We identified the strain LS-4.2 as Penicillium canescens summing its morphological characteristics with the reported DNA sequence. We revealed that the filtrate of a 7-day culture of the fungus suppressed the cell growth of toxic Microcystis aeruginosa. Our results showed that the filtrate caused rapid M. aeruginosa growth inhibition up to complete cell lysis recorded after 4 days. Living fungal mycelia did not suppress the growth of cyanobacterium. According to the results of this study we suppose that strain LS-4.2 may be a potential bioagent in the control of cyanobacterial blooms.

Innovative modernization of Russia’s dairy industry is a key factor in ensuring the country’s food and environmental security in the context of increasing export orientation. The goal of our research is to substantiate the concept for development of the dairy industry in Russia and to develop forecast scenarios for its functioning based on the introduction of the best available technologies. The paper reveals specific features of functioning of the industry and the contradictions they cause. We conclude that effective development of the industry is possible only under balanced state policy that takes into account international experience and the challenges that the industry has to deal with. We analyze the use of the best available technologies in the dairy industry in Russia and propose a model for development of the concept of the dairy industry on the basis of the best available technologies. Our scenarios for development of Russia’s dairy industry are of practical interest, as well as our conclusion that the state policy for the development of this industry should be based on an innovative scenario involving its system modernization, which will help ensure food and environmental security of the country and promote dairy products exports. We note that the development and implementation of the best available technologies at enterprises of the dairy industry with the use of foreign experience and tools of state regulation can serve as a response to the system-wide and rapid transformations that are taking place in the industry at the present time. The material of the paper can be used in the educational process in universities; it is relevant for managers and specialists of the dairy industry and for scientists involved in its development through the use of the best available technologies

The article discusses the importance of an individual approach when considering the time needed for learning basic technical courses of a technical University (such as higher mathematics, physics, etc.) to motivate a student to obtain 100% standard of mastering the educational material using the experience of the Department of mathematics. In the modern conditions of the world of information technologies it is extremely important to teach people how to handle information independently and, what is the most important, to assess it. As you know, universities set a certain studying time for each academic subject fixed by curriculum. But time should not be a constant component. Obviously, such a new approach will require innovation in the methodological literature. Using the experience of the Department of Mathematics of MGSU the author offers methodical developments and research works for studying under the direction of a teacher along with standard digestion of the curriculum.

Abstract Background Accumulating evidences suggest that Hsp 70, the inducible component of Hsp70 family, might release from a living cell. Here we show that a pharmacological inhibitor of phospholipase C activity U73122 caused a 2–4 fold reduction of an intracellular level of Hsp70 in A431 human carcinoma cells. Results A depletion of Hsp70 under U73122 was a result of the protein release since it was detected in cell culture medium, as was established by immunoprecipitation and precipitation with ATP-agarose. The reduction of Hsp70 level was specifically attributed to the inhibition of PLC, since the non-active inhibitor, U73343, had no effect on Hsp70 level. The PLC-dependent decrease of Hsp70 intracellular level was accompanied by the enhanced sensitivity of A431 cells to the apoptogenic effect of hydrogen peroxide. Here for the first time we demonstrated one of the possibilities for a cell to export Hsp70 in PLC-dependent manner. Conclusion From our data we suggest that phospholipase C inhibition is one of the possible mechanisms of Hsp70 release from cells.

Astrocytes are subtypes of glial cells involved in metabolic, structural, homeostatic, and neuroprotective processes that help neurons maintain viability. Insulin-like growth factors IGF-1 and IGF-2 are known to have neuroprotective effects on neurons and glial cells through interaction with specific receptors. IGF forms a complex with IGF-binding proteins (IGFBP) in nervous tissue and is released from the complex via IGFBP proteolysis by specific proteases. It has been reported that IGFBP-2, 5 and 6 are cleaved by specific proteases in the central nervous system (CNS), followed by IGF release; however, it was unknown whether IGFBP-4 was exposed to a particular proteolysis in nervous tissue. Using neurons and astrocytes derived from human induced pluripotent stem cell lines (hiPSC), as well as rat brain-sourced primary neuron-glia cultures, we demonstrated that IGFBP-4 is specifically cleaved in nervous tissue by the Pregnancy Associated Plasma Protein A (PAPP-A) protease and that this cleavage is IGF-dependent. Our results indicate that astrocyte rather than neuron PAPP-A cleaves IGFBP-4 in nervous tissue suggesting that this may be one of the fundamental mechanisms for IGF interchange between these two types of cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the diagnostic capabilities of modifying the standard MRI protocol as part of an interdisciplinary presurgical examination of patients with epileptogenic substrates of unknown etiology., Material and Methods: The results of dynamic MRI of 8 patients with a referral diagnosis of focal cortical dysplasia (FCD) were analyzed. In 7 patients, epilepsy was the reason for a standard MRI of the brain; in another patient with myasthenia, MRI was performed as part of a comprehensive examination. All patients, in addition to standard MRI, underwent a modification of the real-time scanning protocol to include contrast, tractography (DTI), and perfusion techniques (ASL/DSC). In 1 case, with questionable results, the results of a modification of the standard MRI protocol, high-resolution MRI (HR MRI) and hybrid positron emission CT with 11 C-methionine (PET/CT with 11 C-MET) were combined., Results: Seven patients underwent epileptic surgery and 1 patient was operated on for a tumor. In 4 out of 8 patients, based on the results of a modification of the standard MRI protocol, radiological signs of a neoplastic process were identified, which suggested a low-grade tumor. One of them needed PET/CT to confirm the assumption. The results of pathomorphological examination correlated with the direct diagnosis for surgical treatment. One of the 4 patients was suspected to have dysembryoplastic neuroepithelial tumor (DNET) based on the results of the protocol modification, which was also confirmed by pathological examination. In another 4 patients in whom it was possible to narrow the differential between FCD type II and DNET based on the results of the modification, FCD IIb was pathomorphologically verified., Conclusion: The proposed modification of the standard MRI protocol can significantly facilitate the differential diagnosis between the neoplastic and dysplastic origin of an epileptogenic substrate of unknown etiology, which in turn affects the patient's management tactics.

Aim      To study changes in cardiohemodynamic alterations of the myocardium and heart rhythm disorders at 3 and 6 months following the coronavirus infection.Material and methods   EchoCG, ECG Holter monitoring, and Doppler ultrasonography of hepatolienal blood vessels were performed for 77 patients (mean age, 35.9 years) at 3 and 6 months after coronavirus infection. The patients were divided into the following groups: group 1, with injury of the upper respiratory tract; group 2, with bilateral pneumonia (CТ1, 2), and group 3, with severe pneumonia (CТ3, 4). Statistical analysis was performed with a SPSS Statistics Version 25.0 software package.Results At 6 months after the disease onset, the patients noted an improvement of their general condition. In patients with moderate pneumonia, early peak diastolic velocity (p=0.09), right ventricular isovolumic diastolic time (р=0.09), and pulmonary artery systolic pressure (р=0.005) where decreased, while tricuspid annular peak systolic velocity was, in contrast, increased (р=0.042). Both segmental systolic velocity of the LV mid-inferior segment (р=0.006) and the mitral annular Em / Am ratio were decreased. In patients with severe disease at 6 months, right atrial indexed volume was reduced (р=0.036), tricuspid annular Em / Am was decreased (р=0.046), portal and splenic vein flow velocities were decreased, and inferior vena cava diameter was reduced. Late diastolic transmitral flow velocity was increased (р=0.027), and LV basal inferolateral segmental systolic velocity was decreased (р=0.046). In all groups, the number of patients with heart rhythm disorders was decreased, and parasympathetic autonomic influences prevailed.Conclusion      At 6 months after coronavirus infection, practically all patients noted improvement of their general condition; incidence rate of arrhythmia and cases of pericardial effusion were decreased; and autonomic nervous system activity recovered. In patients with moderate and severe disease, morpho-functional parameters of the right heart and the hepatolienal blood flow were normalized, however, occult disorders of LV diastolic function remained, and LV segmental systolic velocity was reduced.

Cardiovascular diseases (CVD) are among the leading causes of death and disability worldwide. Pregnancy-associated plasma protein-A (PAPP-A) is a matrix metalloprotease localized on the cell surface. One of the substrates that PAPP-A cleaves is the insulin-like growth factor binding protein-4 (IGFBP-4), a member of the family of proteins that bind insulin-like growth factor (IGF). Proteolysis of IGFBP-4 by PAPP-A occurs at a specific site resulting in formation of two proteolytic fragments - N-terminal IGFBP-4 (NT-IGFBP-4) and C-terminal IGFBP-4 (CT-IGFBP-4), and leads to the release of IGF activating various cellular processes including migration, proliferation, and cell growth. Increased levels of the proteolytic IGFBP-4 fragments correlate with the development of CVD complications and increased risk of death in patients with the coronary heart disease, acute coronary syndrome, and heart failure. However, there is no direct evidence that PAPP-A specifically cleaves IGFBP-4 in the cardiac tissue under normal and pathological conditions. In the present study, using a primary culture of rat neonatal cardiomyocytes as a model, we have demonstrated that: 1) proteolysis of IGFBP-4 by PAPP-A occurs in the conditioned medium of cardiomyocytes, 2) PAPP-A-specific IGFBP-4 proteolysis is increased when cardiomyocytes are transformed to a hypertrophic state. Thus, it can be assumed that the enhancement of IGFBP-4 cleavage by PAPP-A and hypertrophic changes in cardiomyocytes accompanying CVD are interrelated, and PAPP-A appears to be one of the activators of the IGF-dependent processes in normal and hypertrophic-state cardiomyocytes.

Aim      To study features of diagnosis and treatment of acute myocardial infarction (AMI) in Russian hospitals, results of the treatment, and early and late outcomes (6 and 12 months after AMI diagnosis); to evaluate the consistence of the treatment with clinical guidelines; and to evaluate patients' compliance with the treatment.Material and methods  The program was designed for 3 years, including 24 months for recruitment of patients to the study. The study will include 10, 000 patients hospitalized with a confirmed diagnosis (I21 according to ICD-10) of ST segment elevation acute myocardial infarction (MI) (STEMI) or non-ST segment elevation MI (NSTEMI) based on criteria of the European Society of Cardiology Guidelines on Forth Universal Definition of Myocardial Infarction (2018). The follow-up period was divided into three stages: observation during the stay in the hospital and at 6 and 12 months following inclusion into the registry. The primary endpoint included cardiac death, nonfatal MI during the hospitalization and after one-year follow-up. Secondary endpoints were 6-months and one-year incidence of repeated MI, heart failure, ischemic stroke, clinically significant hemorrhage, unscheduled revascularization after discharge from the hospital, and the proportion of patients who continue on statins, antiplatelet drugs, and drugs of other groups for 6 months and 1 year.Results The inclusion of patients into the registry started in 2020 and will continue for 24 months. By the time of the article publication (June, 2021), more than 2,000 patients will be included.Conclusion      REGION-MI (Russian rEGIstry Of acute myocardial iNfarction) is a multicenter, retrospective and prospective observational cohort study that excludes any interference with the clinical practice. Results of the registry will help to analyze a real picture of medical care provided to patients with myocardial infarction and to schedule ways to improve the situation.

Selenium is an important micronutrient that is essential for the functioning of the human body. Being a component of the active center of several antioxidant enzymes selenium prevents cell injury by free radicals. Decline in selenium-containing enzymes results in progression of oxidative stress and chronic inflammation, which are considered as possible causes for the development of many cardiovascular diseases. This review focuses on mechanisms for prevention of myocardial and vascular injury through the adequate selenium supply to the body. The importance of monitoring and correction of the selenium status in appropriate patients is underlined.

On the example of the diagnosis of the structural basis of focal epilepsy in an adult patient, the possibilities of a multimodal and interdisciplinary approach to diagnosis, combining the latest methods of neuroimaging with the results of neurophysiological examinations, are considered. The interaction and high qualification of specialists in epileptology, neuroradiology and pathomorphology provide a high probability to determine the cause of the focal forms of epilepsy. Along with the introduction of super-inductive MR systems, it is important to use their capabilities correctly and optimize the scanning protocol for the individual characteristics of the patient. With a long-term pharmacoresistant course of focal epilepsy, accompanied by low quality of life, the progression of neurological deficits and the aggravation of cognitive and personality problems in patients, it becomes obvious that these patients, even with negative results of standard MRI, are candidates for a more in-depth comprehensive examination to identify the structural basis of epileptogenesis and subsequent epileptic surgery. However, the problem of epilepsy pseudoresistance should be considered, when a patient with uncontrolled seizures takes antiepileptic drugs for a long time in inadequate dosages. Modern comprehensive diagnostics offers new rational approaches to antiepileptic therapy indication on the part of the doctor, as well as to improve the patient's compliance to the treatment.

Background: Entresto™ is a new heart failure (HF) therapy that includes the neprilysin (NEP) inhibitor sacubitril. One of the NEP substrates is B-type natriuretic peptide (BNP); its augmentation by NEP inhibition is considered as a possible mechanism for the positive effects of Entresto. We hypothesized that the circulating products of BNP proteolysis by NEP might reflect NEP impact on the metabolism of active BNP. We suggest that NEP-based BNP cleavage at position 17-18 results in BNP ring opening and formation of a novel epitope with C-terminal Arg-17 (BNP-neo17 form). In this study, we use a specific immunoassay to explore BNP-neo17 in a rat model and HF patient plasma., Methods: We injected BNP into rats, with or without NEP inhibition with sacubitril. BNP-neo17 in plasma samples at different time points was measured with a specific immunoassay with neglectable cross-reactivity to intact forms. BNP-neo17 and total BNP were measured in EDTA plasma samples of HF patients., Results: BNP-neo17 generation in rat circulation was prevented by NEP inhibition. The maximum 13.2-fold difference in BNP-neo17 concentrations with and without sacubitril was observed at 2 min after injection. BNP-neo17 concentrations in 32 HF patient EDTA plasma samples ranged from 0 to 37 pg/mL (median, 5.4; interquartile range, 0-9.1). BNP-neo17/total BNP had no correlation with total BNP concentration (with r = -0.175, P = 0.680) and showed variability among individuals., Conclusions: BNP-neo17 formation is NEP dependent. Considering that BNP-neo17 is generated from the active form of BNP by NEP, we speculate that BNP-neo17 may reflect both the NEP activity and natriuretic potential and serve for HF therapy guidance., (© 2019 American Association for Clinical Chemistry.)

The literature review systematizes a lot of information on the biological effects of tocotrienols. The effects are described in more details. Vitamin E was discovered at 20s of the last century, but tocotrienols are a less studied part of it. Tocotrienols exhibit cardioprotective, lipid-lowering, antitumor, anti-inflammatory, neuroprotective properties as it has been shown by recent researches. Edible oils (e.g. palm oil, rice bran oil, barley oil, etc.) contain high level of tocotrienols. So, after extraction from plant raw materials they can be used for long-term preventive therapy of many diseases, as well as for the treatment and enhancement of the action of medicinal substances. They can also be used as functional ingredients to stabilize and extend the shelf-life of food products due to their antioxidant properties., (Copyright© GEOTAR-Media Publishing Group.)

The influence of endogenous and exogenous 17-beta-estradiol on the degree of hypoxic pulmonary hypertension (HPH) in male and female Wistar rats has been studied. Endogenous estradiol reduced the right ventricular systolic pressure (RVSP) in normal female rats, but not in male rats. Exogenous estradiol (15 pg/kg for 4 weeks) caused the same effect. The HPH was induced by exposure to intermittent hypobaric hypoxia (10 h a day, 02 = 10%). Two weeks after hypoxia exposure, increased RVSP was more developed in females as compared to males. Comparison of RVSP between hypertensive and normotensive fet'a- le groups showed that the pathology in hypertensive females with retained ovaries is developed more than in ovariectomized ones. Exogenous estradiol exhibi- ted no protective effect in hypoxic ovariectomized female rats. In males, the ovariectomy did not influence the RVSP level, but caused hypertrophy of the right ventricle. In this case, exogenous estradiol led to an increase in RVSP. Thus, endogenous 17-beta-estradiol has a protective effect on the pulmonary blood flow in normal females. In the case of hypoxic pulmonary hypertension, endogenous estradiol enhances the development of this pathology in females and ovariecto- mized males.

Aim: To analyze MR-images of patients with focal epilepsy using a method close to the protocol of epileptic scanning on a MRI-device with the magnetic field tension of 0.4 Tesla., Material and Methods: MRI data of 50 children who underwent examination due to difficult-to-treat or drug-resistant forms of focal epilepsy were analyzed. MRI study was conducted using open-ended device of static magnetic field HITACHI 'APERTO' with the magnetic field tension of 0.4 Tesla. The thickness of the slices and the scan step was performed at 3.0 and 3.5 mm with the use of special positioning of slices in the coronal and axial projections, T2, T1, STIR, FLAIR weighted images (WI) perpendicular and parallel to the long axis of the hippocampus., Results: Potentially epileptogenic structural changes were identified in 37 patients. Abnormalities of brain development of different severity were identified in 16 patients. In 21 cases, the changes were due to the consequences of cerebral vascular catastrophes, neuroinfections, brain traumas affecting the cortical plate. A method close to the epileptic scanning protocol allowed the identification of signs of acute cerebral catastrophes in two patients. In 8 patients, potentially epileptogenic changes after false-negative descriptions of the results of previous MRI studies were newly identified. The most difficult for the diagnosis was the visualization of small structural changes in mediobasal regions of the temporal lobes. Confirmation of this supposition according to the recommended thorough investigation was obtained only in 5 out of 12 patients with suspected small-bore pathological changes in mediobasal temporal regions., Conclusion: Low-tension technique approximated to the epileptic scanning protocol does not allow the reliable diagnosis of small and similar in signal characteristics changes in the visualization of mediobasal temporal lobes regions. It was not possible to reliably differentiate some cortical-subcortical neoplastic formations from various forms of focal cortical dysplasia.

Objective: To analyze MR-images in patients with symptomatic epilepsy associated with the brain tumor., Material and Methods: MRI results of 52 patients with symptomatic epilepsy operated for tumors of supratentorial localization were analyzed. The most epileptogenic tumors with atypical MRI signs and subtle clinical presentation were identified. All patients with tumors were operated using different methods of surgical intervention., Results: Dysembryoplastic neuroepithelial tumors (DNET), diffuse astrocytomas (DA) and gangliogliomas (GG) were the most frequent epileptogenic tumors. In all the cases of DNET and in 4 patients with GG, epileptic seizures were the first, and in 4 of 5 cases of DIO were the only clinical sign of tumor presence. In DNET, DA and GG, there was an iso- or hypointensive signal on T1 WI and a signal varying in intensity from moderate to hyperintense in T2 and FLAIR WI, while in cases with DNET and GG, no mass effect and perifocal edema was practically seen. The so-called «spume-like» (multicystic) structure was most clearly observed in FLAIR WI. No significant changes in the dimensions of the DNET and GG were identified. The combination of DNET with focal cortical dysplasia was noted in one case. In DA, it was difficult to distinguish the perifocal edema from tumorous tissue and normal brain tissues, and the growth potential of malformation was slow., Conclusion: Epileptogenic tumors can imitate the x-ray characteristics of each other, and mimicry to gangliogliomas, oligodendrogliomas and astrocytomas Gr I, II, and others. They are the most frequent causes of symptomatic focal epilepsy. The presence of these malformations is necessary to exclude first of all in all cases of pharmacoresistant epilepsy.

Review of the scientific literature on the evidence of the relationship between palm oil (PO) and its components and adverse effects on human health, on the mechanisms of cholesterol control and risks for development of cardiovascular diseases. PO is solid or semisolid at room temperature and often is used as a natural substitute for partially hydrogenated vegetable oils containing trans fatty acids which increase risks of hypercholesteremia. PO contains both saturated and unsaturated fats as well as substances with antioxidant activity. Taking into account the lipid theory of atherosclerosis pathogenesis, and sn-2 hypothesis, PO was compared with other vegetable oils, like olive, sunflower or soybean oils, and did not show great differences in changes of LDL, HDL or total cholesterol levels. Comparison of diets rich in PO with diets rich in trans fatty acids shows improvement of lipid profiles in groups with PO, and serves as a basis for replacement of trans fatty acids in food with PO and its fractions. In addition to fatty acids content, PO contains several phytonutrients including 4 forms of tocopherols and tocotrienols, carotenoids, sterols, and some others. Most of these compounds are considered beneficial for human health, mainly on account of their antioxidant activity. It is concluded that PO is safe component of food, when we pay attention to the rather high content of saturated fats in it.

The long-term (4 weeks) administration of estradiol (15 μg/kg/day) to ovariectomized female Wistar rats induced hypoxic pulmonary hypertension and significantly (p<0.05) diminished relaxation of perfused serotonin-preconstricted isolated vascular segments of the pulmonary artery in response to estradiol (10(-6) M). At the same time, the isolated segments of systemic popliteal artery demonstrated a diminished response to serotonin and increased relaxation induced by acetylcholine (10(-5) M) or estradiol (10(-5) M) in comparison with preconstricted control vessels. Moderation of responsiveness to estradiol in pulmonary circulation can be one of the factors underlying the pro-hypertensive action of estradiol in female rats with hypoxic pulmonary hypertension.

We have studied the role of female sex hormone estradiol in the development of hypoxic pulmonary arterial hypertension. Previously, it was shown that the development of pulmonary hypertension in Wistar female rats is accompanied by a twofold increase in the estradiol level. Ovariectomy reduces the degree of pulmonary hypertension in these animals. In this work, the effect of various chronic doses of exogenous estradiol (5 and 15 microg/kg per day) on the development of hypoxic pulmonary hypertension in Wistar female rats has been studied. Pulmonary hypertension was induced by exposure to hypobaric hypoxia (10 h a day for 2 weeks) at simulated altitude of 5000 m (O2 concentration reduced to 10%). The administration of estradiol in different doses (5 and 15 microg/kg per day) for 21 day initiated the development of pulmonary hypertension in ovariectomized Wistar female rats.

As we showed previously, administration of estradiol in different doses (5 and 15 mcg per day for 21 day) initiates the development of pulmonary arterial hypertension (PAH) in ovariectomised female Wistar rats. The aim of current study was to analyze the involvement of antagonist of estrogen receptors type a- and beta- ICI 182,780 (fulvestrant) in development of hypoxia-induced pulmonary arterial hypertension. Ovariectomised female rats were separated into 5 groups received subcutaneously for 1 month : 1. Estrogen 15 mcg per day. 2. Estrogen 60 mcg per day 3. Antagonist of estrogen receptors type alpha- and beta- fulvestrant 150 mcg per day. 4. Estrogen 15 mcg/d + fulvestrant 150 mcg/d. 5. Propylenglycol as a control group. PAH was induced by exposure to hypobaric hypoxia. Rats were housed in a hypobaric chamber at simulated altitude of 5000 m, 10 h a day, 2 wk (O2 concentration reduced to 10%). We suppose that the development of pulmonary hypertension in ovariectomised female Wistar rats caused by administration of estrogen (15 mcg and 60 mcg per day for 1 month) is mediated by estrogen receptors type alpha- and beta-.

The aim of the study was to evaluate the effect of chronic inhibition of endothelin-1 (ET-1) synthesis on renovascular hypertension development. Male Wistar rats were subjected to an operation, according to the "1 kidney, 1 clip" method and were given an endothelin-converting enzyme inhibitor PP36 per os with drinking water for 4 weeks. Serum urea rose by 21% in hypertensive rats and by 44% in PP36 treated hypertensive rats. PP36 treatment resulted in blood pressure rise both in the Sham group (compared to the initial blood pressure level) and in hypertensive rats (compared to hypertensive control group). Significant reduction of circulating ET-1 after chronic PP36 administration by 28% was obtained only in normotensive, but not hypertensive rats. Circulating ET-1 was not altered in hypertensive rats, but ET-1 excretion rate was significantly enhanced by 90%, which was abolished by PP36. We suggest that chronic reduction of ET-1 synthesis in the kidney might lead to water and salt retention.

Gender differences play role in pathogenesis and treatment of many cardiovascular diseases. One of these diseases is hypoxia-induced pulmonary hypertension (PHT). The aim of this study was to analyze the involvement of female hormone estradiol in development of hypoxia-induced PHT in female Wistar rats. PHT was induced by exposure to hypobaric hypoxia in an altitude chamber at a simulated altitude of 5000 m (02 concentration reduced to 10 %), 10 h per day for 2 weeks. The development of PHT leads to a twofold increase in the level of estradiol. Ovariectomy decreases by half the level of estradiol and causes significant decrease in hypoxia-induced PHT symptoms.

It is shown that 3-(3-[1,2,4]-triazolo)-oxatriazolium-5-olate (azasidnon-6) can act directly on the vascular wall of isolated segments of caudal ventral artery of SHR rats. Using heme-dependent soluble guanyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), it has been found that one of the possible mechanisms of azasidnon-6 vasodilatory action includes heme-dependent activation of a soluble form of guanylate cyclase.

Background: The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides., Methods: We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP., Results: ProBNP was effectively processed in the circulation into BNP (1-32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively., Conclusions: In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.

An indirect enzyme immunoassay (EIA) using the purified fraction of surface viral glycoproteins (GP) as an antigen for solid phase sensitization was not shown to be a specific method for the differential detection of influenza A(HS) (HS-Ab) virus antibodies (Abs) due to total conservative epitopes in the structure of GPs of influenza A(H5) and A(H1NI) viruses. The cross activity of some monoclonal Abs (MAbs) to influenza A(H5) and A(HIN1) viruses, which had been obtained at the Research Institute of Influenza, was proof of the presence of total immunodominant determinants in the structure of influenza H1 and H5 virus hemagglutinin (HA). In this connection, an EIA, which was based on the competition of influenza A(H5) H5-Ab virus HA-specific MAbs in the test sera for an association with influenza A(H5) virus, was proposed for the subtype-specific detection of H5 Ab. Comparison of the results of competitive EIA (cEIA), microneutralization (MN) test and HA inhibition test (HAIT) (using equine red blood cells) in the examination of sera obtained from 44 volunteers immunized with inactivated vaccine containing influenza A/Indonesia/5/2005 (H5N1) virus showed the high sensitivity and specificity of cEIA in detecting H5-specific Abs. The effectiveness of cEIA for the sera strictly positive for the content of H5 Abs was close to that of MN test and was 9-34% higher than HAIT (depending on those used in the analysis of H5 virus antigens). cEIA may be proposed to assess new influenza vaccines as an additional laboratory test. Since the infectious virus is not used during cEIA, it may be recommended for the serodiagnosis of influenza A(H5) at practical virological laboratories.