Immunotropic effects of vitamin D3 in original rectal suppositories in experimental ulcerative colitis

Increased incidence of ulcerative colitis (UC) is a prerequisite for searching new therapeutic approaches, primarily with an opportunity of site-directed impact on the colon lesion. UC pathogenesis is associated with dysregulated immune response, and limited effectiveness of basic therapy for the disorder. Vitamin D3 exhibits antioxidant, anti-inflammatory, immunomodulatory and other properties, it has been shown to be effective in some autoimmune diseases, thus prompting us to study its effect on immune status in UC. We aimed for studying the effect of vitamin D3, as a component of original rectal suppositories, upon clinical course and indexes of immune status in experimental UC. UC in rats was modeled with 3% oxazolone solution. The vitamin D3-containing suppositories (1500 IU) weighing 300 mg were administered per rectum every 12 hours for 6 days. On days 2, 4 and 6 of UC, the clinical features were assessed as well as blood leukocyte counts, numbers of CD3+, CD45RA+; absorbing and NBT-reducing abilities of blood neutrophils were determined; IgM, IgG, IL-6 and IL-8 concentrations in serum were also studied.The DAI index increased in non-treated UC, along with raised neutrophil numbers in blood, their absorption and NBT-reducing activity was also increased, the total number of lymphocytes, including CD3+, CD45RA+ became higher, serum concentrations of IgM, IgG, IL-6, IL-8 increased. Local use of vitamin D3 in UC reduces DAI parameters, causes decrease in blood neutrophil counts, reducing and partially restoring absorptive and NBT-reducing abilities of neutrophils, decline of total lymphocyte counts in blood, partially restoring the CD3+ and CD45RA+ numbers, causing decline and partial restoration of serum IgM, IgG, IL-6, IL-8 concentrations. An association between clinical signs and indexes of immune status in UC was established under the conditions of vitamin D3 use. Conclusions: The protective effect of vitamin D3 in UC can be mediated by its antioxidant effect, changes in production of immunoregulatory cytokines, modulation of Th1-, Th2-, Th17-dependent reactions and Treg activity, being a pre-requisite for further studies to clarify the mechanism of vitamin D3 immunotropic action in UC,with an opportunity of using it in clinical practice

Melatonin in the dermal film limits the blood lymphocyte death in experimental thermal trauma

According to WHO data, about 11 million people need medical care after burns every year. In the overall structure of burns, the share of thermal trauma (TT) is 80%. Lymphocytopenia in TT is a risk factor for infectious complications and limited repair, and the development of new tools for TT therapy using dermal films is demanded in combustiology. The aim of the study was to evaluate changes in blood lymphocyte parameters, i.e., quantitative composition and their death during experimental thermal damage under the influence of the originally developed dermal film with melatonin (MT) in 49 inbred rats. The grade IIIA TT of 3.5% body surface was modeled by contact with boiling water for 12 s. Dermal films based on sodium carboxymethylcellulose supplemented with MT at a concentration of 0.005 g/g were applied daily for 5 days. The total numbers of lymphocytes, CD45RA+ and CD3+ cells, counts of lymphocytes with signs of partial necrosis, early and late apoptosis were assessed in blood. Relative decrease in the area and rate of the burn wound epithelization were also calculated. In animals with TT, the number of blood lymphocytes decreased on days 5, 10 and 20, including CD45RA+ and CD3+, along with increased amounts of lymphocytes with signs of necrosis, late and early apoptosis. By the term of 20 days, the burn wound area was reduced by 11.5%. Usage of dermal films with MT increased the amount of CD3+ cells in blood on days 5 and 10, CD45RA+ on days 5, 10 and 20, being associated with decreased number of lymphocytes showing signs of early apoptosis on days 5, 10 and 20, as well as features of necrosis and late apoptosis on days 5 following TT, accelerates the healing of a burn wound on days 5, 10 and 20 after TT. with a 20 cent reduction of its area by the day 20. Epithelization rate of the burn wound when applying MT-supplemented dermal film on days 5, 10 and 20 increases, along with higher amounts of CD3+ in the blood, and reduced counts of lymphocytes with signs of early apoptosis

Immunotropic effects of Curcuma longa extract as a component of original rectal suppositories in the dynamics of experimental Сrohn’s disease

Crohn’s disease is an urgent problem of modern gastroenterology due to increasing prevalence, severity of complications and side effects of the basic therapy, in particular upon treatment with 5-aminosalicylic acid (5-ASA). Searching, development and trials of new effective drugs with minimal side effects in Crohn’s disease is an urgent task. Curcuma longa is one of the initial substances containing curcumin with antioxidant, cytoprotective, anti-inflammatory properties. Its effectiveness has been demonstrated in few studies with its systemic use in Crohn’s disease treatment. Our aim was to perform a comparative analysis of curcumin and 5-ASA effect applied as a composition of rectal suppositories, studying clinical signs and indices of immune status in experimental Crohn’s disease. The study was performed on 70 Wistar male rats. Crohn’s disease was modeled by introduction of a 50% alcohol solution of trinitrobenzene sulfonic acid (TNBS) per rectum, and verified by clinical and morphological methods. Rectal suppositories, each containing 50 mg of 5-ASA and original suppositories containing 0.075 mg of curcumin were used over 12 hours during 7 days. The studies were performed on the 3rd , 5th and 7th days of Crohn’s disease.In the course of experimental TNBS-induced Crohn’s disease in animals, an increased frequency of bowel motility, appearance of blood in the stool, decreased body weight progressed from the 3rd to the 7th days of observation, along with increased number in CD3+, CD45RA+ lymphocytes in blood, higher number of segmented neutrophils, lower absorption and NBT-reducing activity of blood neutrophils, increased serum concentrations of IL-23, IgM, IgG. Composition of the new medication form was justified; production technology and standardization of the suppositories containing curcumin for the treatment for Crohn’s disease were developed. Usage of rectal suppositories with curcumin is associated with decreased severity of clinical signs, decrease and partial restoration of segmented neutrophils, CD3+ lymphocyte numbers in blood, recovery of absorption and NBT-reducing ability of blood neutrophils, and decrease of IL-23, IgM, IgG concentrations in serum. The effectiveness of rectal suppositories with curcumin is compared to the effectiveness of the use of rectal suppositories with 5-ASA in terms of disease activity index, the number of neutrophils and CD3+ lymphocytes in the blood, serum concentrations of IL-23, IgM and IgG, in, at lesser extent, in terms of absorption and NBT- reducing ability of blood neutrophils.The composition and production technology of rectal suppositories with curcuminwas developed; the leukocyte populations, CD3+, CD45RA+ lymphocytesin blood were assesed, neutrophil absorption and NBT-reducing ability, IL-23, IgM and IgG concentrations were determined; the use of rectal suppositories with curcumin in experimental Crohn’s disease is comparable with the effectiveness of rectal suppositories with 5-ASA

Pretest probability of coronary artery disease as a factor for optimizing invasive diagnostics in routine clinical practice

According to the European Society of Cardiology guidelines, patients with chest pain requires the calculation of pretest probability (PTP) of coronary artery disease (CAD), followed by the identification of diagnostic tactics.Aim. To analyze the registry of patients with stable CAD in order to assess the frequency of PTP calculation, as well as the validity of diagnostic tactics choice depending on its level.Material and methods. The data of the registry of patients with stable CAD for the periods from 2012 to 2014 and from 2017 to 2019 were analyzed. We assessed the number of CAD patients, proportion of men, and distribution of patients depending on angina functional class. In addition, data on PTP calculation, as well as distribution of patients and diagnostic strategy selected depending on its value was analyzed. To assess differences (p) in pairwise comparisons, Student’s t-test was used. Differences were considered significant at p<0,05. Statistical analysis was performed using Microsoft Office Excel 2010 (Microsoft, USA) and STATISTICA 6.0 (StatSoft Inc., USA).Results. In 2017-2019, the number of detected CAD cases and proportion of men increased. In both time periods, an insufficient level of calculating PTP of CAD remains. In patients with intermediate PTP, 15-85% of priority tactics are invasive interventions, and with high PTP, the percentage of invasive methods does not reach the proper level, which does not correspond to modern guidelines for the management of CAD patients and leads to misappropriation of funds and healthcare resources.Conclusion. According to medical records, PTP can be determined in less than half of patients. In CAD patients with intermediate PTP, non-invasive studies are not carried out in full, since coronary angiography is preferred. In patients with a high PTP, invasive diagnostics is insufficient

Implementation of 14 bits floating point numbers of calculating units for neural network hardware development

An important aspect of modern automation is machine learning. Specifically, neural networks are used for environment analysis and decision making based on available data. This article covers the most frequently performed operations on floating-point numbers in artificial neural networks. Also, a selection of the optimum value of the bit to 14-bit floating-point numbers for implementation on FPGAs was submitted based on the modern architecture of integrated circuits. The description of the floating-point multiplication (multiplier) algorithm was presented. In addition, features of the addition (adder) and subtraction (subtractor) operations were described in the article. Furthermore, operations for such variety of neural networks as a convolution network - mathematical comparison of a floating point ('less than' and 'greater than or equal') were presented. In conclusion, the comparison with calculating units of Atlera was made

Deep Learning for Single-Molecule Science

Exploring and making predictions based on single-molecule data can be challenging, not only due to the sheer size of the datasets, but also because a priori knowledge about the signal characteristics is typically limited and poor signal-to-noise ratio. For example, hypothesis-driven data exploration, informed by an expectation of the signal characteristics, can lead to interpretation bias or loss of information. Equally, even when the different data categories are known, e.g., the four bases in DNA sequencing, it is often difficult to know how to make best use of the available information content. The latest developments in Machine Learning (ML), so-called Deep Learning (DL) offers an interesting, new avenues to address such challenges. In some applications, such as speech and image recognition, DL has been able to outperform conventional Machine Learning strategies and even human performance. However, to date DL has not been applied much in single-molecule science, presumably in part because relatively little is known about the 'internal workings' of such DL tools within single-molecule science as a field. In this Tutorial, we make an attempt to illustrate in a step-by-step guide how one of those, a Convolutional Neural Network, may be used for base calling in DNA sequencing applications. We compare it with a Support Vector Machine as a more conventional ML method, and and discuss some of the strengths and weaknesses of the approach. In particular, a 'deep' neural network has many features of a 'black box', which has important implications on how we look at and interpret data

Clinical and morphological characteristics of experimental ulcerative colitis in the conditions of using original rectal suppositories with vitamin D3

The aims was to study the effect of vitamin D3 in the composition of original rectal suppositories on the clinical status and morphology of the lesion of colon in experimental UC.Цель работы: исследовать влияние витамина D3 в составе оригинальных ректальных суппозиториев на клинический статус и морфологию участка повреждения толстой кишки при экспериментальном язвенном колит

Induced polarization of {\Lambda}(1116) in kaon electroproduction

We have measured the induced polarization of the ${\Lambda}(1116)$ in the reaction $ep\rightarrow e'K^+{\Lambda}$, detecting the scattered $e'$ and $K^+$ in the final state along with the proton from the decay $\Lambda\rightarrow p\pi^-$.The present study used the CEBAF Large Acceptance Spectrometer (CLAS), which allowed for a large kinematic acceptance in invariant energy $W$ ($1.6\leq W \leq 2.7$ GeV) and covered the full range of the kaon production angle at an average momentum transfer $Q^2=1.90$ GeV$^2$.In this experiment a 5.50 GeV electron beam was incident upon an unpolarized liquid-hydrogen target. We have mapped out the $W$ and kaon production angle dependencies of the induced polarization and found striking differences from photoproduction data over most of the kinematic range studied. However, we also found that the induced polarization is essentially $Q^2$ independent in our kinematic domain, suggesting that somewhere below the $Q^2$ covered here there must be a strong $Q^2$ dependence. Along with previously published photo- and electroproduction cross sections and polarization observables, these data are needed for the development of models, such as effective field theories, and as input to coupled-channel analyses that can provide evidence of previously unobserved $s$-channel resonances.Comment: 13 figure

Towards a resolution of the proton form factor problem: new electron and positron scattering data

There is a significant discrepancy between the values of the proton electric form factor, $G_E^p$, extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of $G_E^p$ from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector. This novel technique allowed us to cover a wide range in virtual photon polarization ($\varepsilon$) and momentum transfer ($Q^2$) simultaneously, as well as to cancel luminosity-related systematic errors. The cross section ratio increases with decreasing $\varepsilon$ at $Q^2 = 1.45 \text{ GeV}^2$. This measurement is consistent with the size of the form factor discrepancy at $Q^2\approx 1.75$ GeV$^2$ and with hadronic calculations including nucleon and $\Delta$ intermediate states, which have been shown to resolve the discrepancy up to $2-3$ GeV$^2$.Comment: 6 pages, 4 figures, submitted to PR