bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound-guided estimation of gastric residual volume using Perlas’s formula: A validation study in patients
Authors: Khandekar Sayali S. , Doctor Jeson R. , Awaskar Shilpa K. , Alex Nidhin K. , Medha Lipika R. , Ranganathan Priya
Published: April 2022

Background and Aims:

Bedside ultrasound (US) is used to evaluate gastric residual volume (GRV) and assess aspiration risk. We examined the accuracy of US-guided measurement of GRV using Perlas’s formula, by two trained anaesthesiologists, in patients who had consumed different types and volumes of fluids.

Methods:

Patients with no risk factors for delayed gastric emptying were included. Each assessor independently determined the baseline US-guided GRV. The patients were randomly allocated to receive no drink or 100 or 200 mL of water or milk. US-guided GRV was re-assessed within 5 min after the intervention. Investigators were blinded to the measurements performed by each other and to the randomisation arm. The primary outcome was the agreement between actual volumes consumed and estimated change in GRV.

Results:

Agreement between actual volume consumed and estimated change in GRV was poor [Intra-class correlation coefficient (ICC) 0.46, 95% confidence interval (CI) 0.09 to 0.72; P = 0.09 for assessor 1 and ICC 0.37; 95% CI 0.02 to 0.66; P = 0.03 for assessor 2].

Conclusion:

US-guided GRV measurements using Perlas’s formula, performed by trained anaesthesiologists may not be a reliable measure of GRV.
Outcomes and Factors Associated with Extubation Failure in Preterm Infants
Authors: Al-Matary Abdulrahman , AlOtaiby Shahad , Alenizi Saad F
Published: April 2022

Background:

Preterm infants usually have multiple complications, mainly due to their low birth weight. Multiple factors may lead to the need for intubating preterm infants. However, some infants may suffer from difficult extubation and failure to extubate from ventilation. This failure can result in increased morbidity or mortality.

Objective:

This study aims to evaluate the factors contributing to the failure of extubation and their outcomes in preterm infants.

Materials and Methods:

This is a retrospective descriptive cohort study that included records from neonatal intensive care unit for patients who had failed extubation from January 2014 to December 2020. The data included information about patients' demographics, pregnancy and delivery, description of ventilation course, and outcomes. SPSS version 26 was used for statistical analysis.

Results:

Seventy-seven infants were included. Males represented 61%, birth weight 37.7% had a <1 kg, 45.5% of the patients had a gestational age <28 weeks. The mean duration for mechanical ventilation was 19.21 ± 3.2 days, while the duration of intubation was 26.53 ± 2.3 days, and the average length of hospital stay was 86.2 ± 6.7 days. Male gender (P = 0.023), birth weight less than one kilogram (P = 0.004), gestational age <28 weeks (P = 0.033), sedation (P = 0.043), caffeine administration (P = 0.048), and a previous history of extubation failure (P = 0.036), lower hemoglobin levels (P = 0.039), lower APGAR score at 5 min (P = 0.013), and a previous history of extubation failure (P = 0.036) were significant factors associated with failure of extubation. Patent ductus arteriosus presence is not associated with failure of extubation. Mortality was 24.7% and prolonged length of hospital stay was significantly higher in babies with failure of extubation.

Conclusion:

Failure of extubation is more with babies received sedation, male gender, birth weight <1 kg, lower gestation age, and lower Apgar at 5 min. Patients with failing extubation have high in-hospital mortality and prolonged hospital stay.
A Case Study of Medicinal Plants and Their Uses by the Sundar Haraicha Nagarpalika Community in Morang District, East Nepal
Authors: Mandal Honey Raj , Katel Shambhu , Baidhya Shulov , Kattel Sujata , Katuwal Amrit
Published: April 2022

Background:

Nepal is considered as a staple area for wild as well as local medicinal plants. Traditional botanical medicine is the primary mode of health care for most of the people. Several case studies were conducted across the country but some of them were unexposed. So such studies were conducted in order to reveal the importance of locally available medicinal plant species which leads to the discovery of useful drugs and socio-economic development of the community.

Objectives:

The main objective of this study is to evaluate the importance of each plant species and reveal the purposes to use of the medicinal plants by the local community.

Materials and methods:

Data was collected in the Morang district of East Nepal. Informal meetings, group discussion, participants observations and schedule surveys were primary sources of data collection. A total of 60 respondents were questioned through an interview by the semi structured English language questionnaire.

Result:

A total of 60 respondents were recorded. 37 species of medicinal plants belonging to 30 families and 35 genera were documented. The majority of them were herbs and these herbs were able to cure fever, headache, stomachache, cuts and wounds, snake bite etc. Additionally, 26% of medicinal plants are used to treat ailment in the peoples, 48% for both animals and humans, and 25% for marketing.

Conclusion:

Through this case study, it leads to discovering high priority medicinal plants. Similarly, high potential for the establishment of crude drugs and socio-economic development.
ROS1 Rearranged Pulmonary Sarcomatoid Carcinoma
Authors: Devi H. J. , Arjun A. S. , Maka Vinayak
Published: April 2022

Pulmonary sarcomatoid carcinoma (PSC) is a rare type of non-small cell lung cancer which contains poorly differentiated cells and sarcoma or sarcomatoid components (spindle and/or giant cells). Most of the cases are peripherally located and usually present as a large lung mass. We report a case of PSC in a 42-year-old male with massive pleural effusion as initial presentation. Therapeutic pleurocentesis showed exudative lymphocyte predominant pleural fluid. The diagnosis of PSC could be arrived at with medical thoracoscopy, biopsy and immunohistochemical staining. The next generation sequencing assay of gene panel revealed ROS1 positive status. The patient responded well to crizotinib, till the last follow-up of 21 months from the start of treatment.
Extraosseous Ewing Sarcoma
Authors: Sai Ram Krishna , Lokesh K. N. , Dasappa Lokanatha , Babu M. C. Suresh , Rajeev L. K. , Jacob Linu Abraham
Published: April 2022

Background:

Extraosseous Ewing sarcoma (EOES) is the rare soft-tissue counterpart of Ewing sarcoma (ES) of bone. However, studies on clinical behavior and outcome of EOES are scarce. In this retrospective study, we described the pattern of clinicodemographic characteristics, treatment, and outcomes of EOES and explored predictors of outcomes.

Materials and Methods:

A total of 46 diagnosed EOES patients were treated at our institute from September 2017 to January 2020. The detailed data were retrieved from hospital records and were analyzed. Progression-free survival (PFS) was estimated by the method of Kaplan and Meier curve. Comparison of different parameters for PFS was calculated by using log-rank test.

Results:

The mean age at diagnosis was 29.6 years with a male-to-female ratio of 1.4:1. The most common primary site of location for EOES was lower limb (n = 14), followed by retroperitoneum (n = 13) and trunk (n = 10). Seven (15.2%) patients presented with upfront metastasis and the rest 39 cases were nonmetastatic. Treatment outcome was evaluated in 43 patients (38 nonmetastatic and 5 metastatic) in terms of median PFS (mPFS). Extremity EOES in comparison to nonextremity (axial) EOES (P = 0.030) and localized versus upfront metastatic EOES (P = 0.001) had better mPFS. The localized EOES patients who received surgical treatment approach had higher mPFS than those who received nonsurgical treatment (18 months versus 14 months; P = 0.009). EOES patients with subcutaneous (SC) lesions had a trend of higher mPFS than other patients (19 months versus 15 months; P = 0.055). We did not find any difference in mPFS for gender and size of the tumor at presentation.

Conclusions:

Lower limb and retroperitoneum are the common primary sites of presentation for EOES. EOES patients with extremity location, SC lesion in comparison to deeper presentation, upfront nonmetastatic, and those receiving surgical treatment approach performed better.
Primary Small-cell Neuroendocrine Carcinoma of the Gallbladder with Bone Metastasis
Authors: Anand Abhishek , Ali Mohammad , Qayoom Sumaira , Singh Geeta
Published: April 2022

Primary small-cell neuroendocrine carcinomas (NEC) of the gallbladder (GB) are rare with aggressive behavior. It has high malignancy potential with a low survival rate. In this case report, we present a case of primary small-cell NEC of GB in a 43-year-old female who presented with complaints of constipation, upper abdominal pain, and poor oral intake which was identified as a GB mass with liver nodularity on ultrasonography. It was subsequently diagnosed as a case of primary small-cell NEC of GB with liver and bone metastasis on contrast-enhanced computed tomography and core needle biopsy obtained from the left iliac bone. In view of severe jaundice, endoscopic retrograde cholangiopancreatography dilatation and stenting was done followed by palliative chemotherapy and radiotherapy. This case is unique in presenting with liver and bone metastases both instead of only liver metastasis as is commonly seen. Moreover, a sample for histopathological diagnosis was also obtained from a bony site rather than the liver as is the norm.
Analysis of PIK3CA Mutation Concordance and Frequency in Primary and Different Distant Metastatic Sites in Breast Cancer
Authors: Park Jieun , Cho Soo Youn , Chang Eun Sol , Sung Minjung , Song Ji-Young , Jung Kyungsoo , Kim Sung-Su , Shin Young Kee , Choi Yoon-La
Published: April 2022

Purpose The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved.Materials and Methods Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. Results After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. Conclusion The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.
NEW STRAIN OF MUTANT MICE CHARACTERIZED BY SELECTIVE RESISTANCE TO ONE OF TWO SEPTIC SHOCK PROTOCOLS
Authors: Astrakhantseva I. V. , Gladkova L. S. , Vasilenko E. A. , Tarabykin V. S. , Drutskaya M. S. , Nedospasov S. A.
Published: April 2022

More than 40 years ago ethyl nitrosoеurea was identified as a powerful mutagen for mammalian germ cells resulting in random point mutations in gamete DNA. This feature allowed the use of this mutagen for genetic studies on the mechanisms of various pathological and physiological processes in model organisms. In our study genome-wide mutagenesis in C3H mice by ethyl nitrosourea followed in generation F3 by selection of animals resistant to acute lethal hepatotoxicity caused by a combination of E. coli lipopolysaccharide (LPS) and D-galactosamine (D-gal). Tumor necrosis factor (TNF) is known to be a critical mediator of this pathology. Exposure to D-galactosamine increases sensitivity of hepatocytes to TNF leading to their necrosis and/or apoptosis. After double LPS/D-gal screening in F3 several mice resistant to LPS/D-gal-induced hepatotoxicity were identified, and became the founders of the corresponding “mutant” families. Using outcrossing to C57BL6 background followed by intercrossing, generations F5 and F7 were obtained. Among families of mutant animals only one family showed the resistance to the combination of LPS and D-gal, but sensitivity to TNF-D-galactosamine. This phenotype showed approximately Mendelian inheritance consistent with the recessive mutation hypothesis. This latter fact was confirmed by the sensitivity of mice from “heterozygous generations” (F4 and F6) to lethal LPS/Dgal hepatotoxicity. Primary bone marrow macrophages obtained from half of the mutant mice showed significantly reduced levels of TNF after LPS stimulation in vitro. At the same time, the serum TNF levels 1 hour after the administration of a non-lethal LPS dose did not differ in the mutant family mice and wild-type mice. These results implicate a recessive mutation either in innate TLR4-mediated signaling pathway, including proteins associated with LPS transfer, adapter molecules, components of kinase signaling cascades, transcription factors, or in enzymes involved in regulation of TLR4 cascades, such as components of the ubiquitin cycle, or in genomic regulatory sequences that control the expression of one of these genes, including the tnf gene.
Dynamics of cellular factors of innate immunity and antioxidant protection in the patients with chronic recurrent vulvovaginal candidosis upon exposure to cavitated physiological solution
Authors: Sorokin Yu. A. , Gizinger O. A.
Published: April 2022

Dysfunction of colonization resistance factors at the mucous membranes of genitourinary system during adhesion of Candida fungi is a common pathogenic situation leading to impairment of the mucous membrane regeneration, unsuccessful attempts at in vitro fertilization (IVF), increased risk of complications during gestation. The aim of present study was to substantiate the opportunity of complex therapy for chronic vulvovaginal candidiasis using cavitated saline and usage suppositories with alpha-2b human recombinant interferon a (Viferon LLC, Russia). The study involved 90 women at the age of25.45±7.16 years, with clinically and laboratory confirmed recurrencies of chronic vulvovaginal candidiasis observed, on average, 5.55±0.45 times. Group 1 consisted of 30 women with C. albicans infection of urogenital tract, at the mean age of 27.11±1.52 years, who received therapy with fluconazole (150 mg once every 7 days). Group 2 consisted of 30 women with C. albicans infection of mucous membranes, mean age 27.31±1.99 years, treated with Fluconazole (150 mg 1 time in 7 days, and 5-min. irrigation of vagina with ultrasonicated saline solution, 7 days; Low-intensity ultrasound exposure was performed using the Fotek AK100-25 hardware complex, ultrasonic vibration frequency of 25 kHz (Yekaterinburg, Russia). Group 3 consisted of 30 women whose treatment included Fluconazole (150 mg once every 6 days), irrigation of mucous membranes with ultrasonicated cavitated solution and subsequent administration of suppositories containing Viferon® 500,000 IU (1 suppository daily for 7 days). Biochemical studies included determination of isopropanol- and heptane-soluble primary, secondary end products of lipid peroxidation. Activity of the antioxidant system was studied by determination of superoxide dismutase, glutathione peroxidase, ceruloplasmin, vitamin C. Qualitative and quantitative characteristics of neutrophilic granulocytes from vaginal secretions were evaluated by testing phagocytic activity, reduction of nitroblue tetrazolium compound to diformazan. The studies of IL-8, TNFα, IL-2, and IL-10 cytokines were carried out in cell-free supernates of vaginal secretions by ELISA test systems (LLC “Vector Best”, Novosibirsk). Results: upon therapeutic exposure to low-frequency ultrasonic cavitation combined with antioxidant drug, we have observed a decreased local concentration of pro-inflammatory cytokines, the balance of lipid peroxidationantioxidant defense system was restored, and functional metabolic status of the phagocytes in vaginal secretions was normalized.
Studies of immunological and microbiological efficiency of the therapy of curcumin and methionine in the developed capsules
Authors: Khisamova A. A. , Gizinger O. A. , Kornova N. V. , Zyryanova K. S. , Korkmazov A. M. , Beloshangin A. S.
Published: April 2022

Curcumin is a polyphenolic compound, the main component of the Curcuma longa rhizome. Recently, there is growing interest to studies of this new, inexpensive and safe substance that may be used to treat various diseases. Curcumin is widely used in medicine due to its therapeutic efficacy and safety. Its usage in therapeutic practice as a dietary supplement has shown that curcumin exhibits antioxidant and immunomodulatory effects. Data from clinical studies have shown its pharmacokinetic, pharmacodynamic profile and potential use of curcumin in humans for treatment of various diseases, even at the early stages of treatment. Purpose of the study: analysis of immunomodulatory and microbiological properties when using the original grained preparation containing curcumin and methionine. It is suggested to have a regulatory effect by modulating microbial richness, diversity and composition of intestinal microflora. Analysis of immunomodulatory and microbiological activity of the components in the developed dosage form of the capsules with curcumin and methionine was carried out in vitro and in vivo. Functional and metabolic properties of neutrophils were determined with addition of its components, i.e., curcumin and methionine. The analysis of intensity and activity of neutrophils was carried out using the NBT-test. The analysis showed that simultaneous incubation of peripheral blood neutrophils from ICR (CD-1) mice with curcumin and methionine leads to an increase in spontaneous and induced NBT-reducing activity, an increase in the functional reserve and phagocytic activity of peripheral blood neutrophils in mice. A study of the modulating effects of oral intake of curcumin and methionine, which are part of the dosage form, on the intestinal microbiota of ICR (CD-1) mice was carried out. It was found that curcumin, together with methionine, affects the number of some representative families of intestinal microbial communities: in total, there were 640 common operating taxonomic units. between the curcumin-methionine and control groups, 65 were unique in the curcumin-methionine group and 93 in the control group. Given the direct link between gut microbiota and certain diseases, these results may help to interpret therapeutic benefits of curcumin with methionine. The results of the study showed that the developed dosage form, which contains curcumin and methionine, shows antioxidant and immunomodulatory effects, which can be potentially used to treat diseases associated with the effects of oxidative stress on the organism.
Reaction to damage of connective tissue in immunoprivileged organ (testis)
Authors: Khramtsova Yu. S. , Tyumentseva N. V. , Artashyan O. S. , Yushkov B. G.
Published: April 2022

Microenvironment of sperm and its precursors includes various immune cell populations. This indicates not only their importance for immune privileged state within testes, but it concerns a regulatory role of these structures in performance of the most important physiological functions. Despite sufficient knowledge on the immune privileged state in the organ, the regulatory function are scarcely studied, and existing literature virtually does not cover the issues of local spermatogenesis regulation by various components of testicular microenvironment in the course of their regeneration. Purpose of the present study was to define the reactions of connective tissue in rat testis following traumatic lesion. Materials and methods: the study was carried out in mature male Wistar rats. Experimental animals were divided into 2 groups: intact animals and animals with blunt trauma to the left testicle. The animals were removed from the experiment on the 7th and 30th days. Blunt trauma was simulated by squeezing the organ with forceps with a force of 15 N for 3 seconds. For histological examination, the testes were excised, preparations were made by the standard scheme, stained with hematoxylin/ eosin, toluidine blue (to identify mast cells), and according to Van Gieson (to detect collagen fibers). Distinct components of connective tissue and spermatogenesis were evaluated in testicular preparations. Quantitative indexes were calculated using the ImageJ program. Total testosterone levels in the blood were determined by chemiluminescence technique. Statistical evaluation was performed with Statistica 8.0 software. Comparison of groups was performed using Mann-Whitney test. We have found that restoration of spermatogenesis in the damaged testis did not occur within 30 days after the injury. While the reaction of connective tissue was noted in the both testes, it was more pronounced in the damaged organ, and manifests as changes in testicular microvasculature, stimulation of fibroblastic response, multidirectional effects of mast cells and Leydig cells, depending on the duration of exposure. Changes in various components of microenvironment in the damaged testis led to similar changes in the intact organ. The mechanism of this change is usually associated with effect of antisperm antibodies and development of autoimmune processes, but another possible mechanism for impairment of spermatogenesis in the second paired intact organ may include effects of connective tissue microenvironment upon the spermatogenic epithelial cells.
In vitro induction of regenerative and osteogenic activity of PDLSC cells
Authors: Sukhovey Yu. G. , Kostolomova E. G. , Unger I. G. , Akuneeva T. V.
Published: April 2022

The restoration of damaged tissues in periodontal diseases is not only a medical problem, but also a social one. Periodontal diseases often entail the loss of a large number of teeth (more than with any other disease of the dentition), as a result, a violation of the act of chewing and speech, a negative effect on the general condition of the body and, as a result, a decrease in the quality of human life. Purpose of the study: to study the regenerative activity of a lyophilized extract of a chicken embryo of various concentrations in the composition of hyaluronic acid in relation to the culture of PDLSC cells in an in vitro experiment. Comparison groups: A solution of 1% unmodified hyaluronic acid containing lyophilized chicken embryo extract in three concentrations: 300 μg/ml, 150 μg/ml, 75 μg/ml. As a control, 1% solution of unmodified hyaluronic acid. Hyaluronic acid is a natural substance that is an important component of the extracellular matrix as a mineralized and non-mineralized tissue. Its use attracts the attention of specialists as an object capable of acquiring new properties with its various modifications. In our laboratory studies, stem cells from a culture of human periodontal disease were used. Periodontitis stem cells (PDLSC periodontal ligament) were discovered in 2004. Cell adhesion and tissue penetration were investigated by impedimetry. Analysis to assess cell viability was carried out using a solution containing a water-soluble tetrazolium salt. Differentiation of osteogenic direction without induction was measured three weeks after dilution of stem cells in traditional culture medium. Staining was carried out according to the Koss method. To assess mineralization, cells were stained with alizarin red, followed by assessment of calcium deposition in them. It was found that the resulting PDLSC cell population during the experiment was heterogeneous and showed healthy fibroblast morphology in all three study groups. Lyophilized extract of chicken embryo as part of a preparation based on hyaluronic acid does not significantly affect the survival and proliferation of PDLSC cells, however, at high concentrations (150 μg/ml and 300 μg/ml) it induces osteogenic activity of cells, increases mineralization without causing calcium deposition, which indicates regenerative activity. Osteogenic transdifferentiation is an attractive way to create cells of osteogenic cellular origin. The results of our study show that they can be used to model bone diseases.
Cytokine profile of seminal plasma and effectiveness of assisted reproductive technology programs
Authors: Arefieva A. S. , Babayan A. A. , Kalinina E. A. , Nikolaeva M. A.
Published: April 2022

Increasing evidence shows that seminal plasma is among the most important immunoregulatory factors in female reproductive function. We suggest that the favorable effect of the partner’s seminal plasma (SP) upon pregnancy occurence in women during the cycle of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) may be provided by the balanced content of Th1/Th2-dependent seminal cytokines. Otherwise, in case of pathologic changes in SP composition, it may negatively affect the IVF efficiency. Our aim was to determine whether the levels of seminal IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-18, IFNγ, TNFα, TNFβ and TGF-β1 are associated with pregnancy establishment in female patients exposed to seminal plasma during IVF/ICSI cycle.Twenty-eight female patients were exposed to seminal plasma via sexual intercourse before the day of oocyte retrieval, and also underwent intravaginal application of seminal plasma just after transvaginal puncture and oocyte retrieval. Quantitative measurement of seminal cytokines was performed by FlowCytomix™ technology. IL-1, IL-18 and TNFβ concentrations were significantly higher in non-pregnant group (p = 0.011; p = 0.030 and p = 0.008, respectively). The contents of IL-2, IL-6, IL-18 and TNFβ per ejaculate were also significantly higher in non-pregnant group (p = 0.020; р = 0.042; р = 0.030 and р = 0.004, respectively). We conclude that elevated concentrations of proinflammatory cytokines in seminal plasma, as well as their total excessive content per ejaculate may have an adverse effect on implantation and pregnancy establishment.
Effect of antiplague vaccination on phagocytic activity of human blood granulocytes
Authors: Kravtsov A. L. , Klyueva S. N. , Kozhevnikov V. A. , Kudryavtseva O. M. , Bugorkova S. A.
Published: April 2022

Anti-plague vaccination stimulates phagocytosis of Yersinia pestis cells by blood leukocytes of laboratory animals. However its effect on the phagocytic activity of human white blood cells towards plague microbes has not been studied. In this work, flow cytometry was used to study phagocytic activity of blood granulocytes towards Y. pestis, Escherichia coli and Staphylococcus aureus in the people vaccinated, or not vaccinated against plague. These persons inhabited the territories of natural plague foci in Russian Federation. The results of phagocytic activity were evaluated in microvolumes of whole blood. The induced IFNγ production was evaluated in blood by enzyme immunoassay technique, and the titers of specific antibodies to plague-specific F1 antigen were determined in blood serum samples. It was found, that the subjects who have never been vaccinated against plague had 3-fold lower granulocyte phagocytic activity towards Y. pestis than the persons repeatedly vaccinated with live plague vaccine, and 5-fold lower than phagocytosis of E. coli and S. aureus. The next annual revaccination caused additional stimulation of in vitro phagocytic capacity of blood leukocytes with respect to plague microbes. Individual values of phagocytic indices correlated with serum antibody titers (r = 0.65, p = 0.0004), and with levels of IFNγ production (r = 0.73, p = 0.0004). Thus, the obtained data confirmed dependence between phagocytic activity of human blood leukocytes and the pathogen type, thus allowing to demonstrate a connection between activated phagocytic response to Y. pestis cells in live plague-vaccinated individuals with other immune indexes of vaccine efficiency (specific antibodies to F1, induced IFNγ production). Further research in this direction will bring us closer to development of an informative test for assessing the intensity of antiplague immunity.
Dynamics of the level of cytokines in the isolated femoral fracture under conditions of system ozone therapy
Authors: Abramov K. S. , Davydova E. V. , Osikov M. V.
Published: April 2022

A close link between processes of immune-based and osteogenesis, influence of immune system on reparative processes after a traumatic femur fracture, as well as state of increased afferent signals emitted by intraosseous receptors and hyperstimulation of immune cells during trauma accounts for feasibility of using efferent multimodal therapy interventions, which may be accomplished by medical ozone. The aim of the study was to assess dynamic changes in pain syndrome and level of pro- and anti-inflammatory cytokines in isolated femur fracture treated with systemic ozone therapy. The study group coprised 32 male patients with isolated femur fracture, average age 44.2±2.4 years. Starting from day 2 after surgical treatment, all patients received standard anticoagulant treatment and antibiotic therapy, 16 patients additionally received ozone therapy applied as small autohemotherapy (MAGT) at ozone therapeutic unit by using ozone destructor UOTA-60-01 “Medozon” manufactured by Medozon LLC, Moscow. Ozone concentration in ozone-oxygen mixture was 20 mg/l, per 10 ml-volume, applied as 7-9 injections course every other day. Patient-provided assessment of pain level in all groups was investigated by using a visual analogue pain scale. Concentrations of IL-6 and IL-4 cytokines were measured by using standard test systems (pruchased from Vector-Best JSC, Novosibirsk). Statistical data processing was carried out by using software package Statistica 10.0. The subjective pain level prior to the onset of the course ozone therapy and 2 days after surgical treatment was higher than average level after the end of MAGT course, pain level decreased to low level and significantly differed from that one before surgery, which indicates developed analgesic effect after systemic ozone therapy, likely associated with oxidative modification of inflammatory mediators. The level of pro-inflammatory cytokine IL-6 in patients with IPPK during systemic ozone therapy significantly decreased, which indicates some normalizing effect induced by ozone therapy on parameters of immunocyte secretory activity and prevents ovgert effects triggered by “cytokine storm”. Concentration of IL-4 vs after traumatic femur damage did not significantly differ among patient groups, except for differences with control group. Spearman correlation analysis revealed high degree of dependence between pain intensity and level of pro-inflammatory cytokines, whereas ozone therapy led to decreased pain intensity in lesion site and directly correlated with decreased IL-6 concentration. Thus, use of ozone at therapeutic concentrations limits excessive reactions of innate immunity that can lead to massive tissue damage in early stages of the posttraumatic process.
State of hyperglycemic and immunomodulator-treated peripheral blood lymphocytes
Authors: Gette I. F. , Danilova I. G.
Published: April 2022

A level of peripheral blood lymphocytes, their functional activity and particularly produced range of secreted cytokines underlie severity of autoimmune process in diabetes mellitus (DM) against islet β-cells and other body cells. Because cytokine production is coordinated by macrophages and may also depend on accessibility lymphocyte nucleic acids, we aimed at examining level of nucleic acids in blood lymphocytes as well as cytokine production in rats with alloxan-induced diabetes treated with immunomodulatory 3-aminophthalhydrazide (3-APH). Type 1 DM was modeled in male WISTAR rats by intraperitoneally administered alloxan at a dose of 300 mg/kg followed by inoculating 3-APH (2 mg/kg, in total 20 intramuscular injections). It was found that modeled diabetes was accompanied by increased number of peripheral blood lymphocytes and their bone marrow precursors, coupled to higher DNA amount in blood lymphocytes and associated with increased IL-6 and TNFα production. Administration of 3-APH to diabetic rats contributed to decreased number of peripheral blood lymphocytes and related DNA level likely resulting in decreased level of pro-inflammatory cytokine IL-6 in the blood serum and contributing to corrected hyperglycemia.
Experience of applying flow cytometry to assess immunologic reactivity in subjects with increased blood vanadium concentration
Authors: Dianova D. G. , Dolgikh O. V. , Alekseev V. B.
Published: April 2022

Environmental pollution with external vanadium results in its accumulation in human biological media and alters ability of human body to properly react to negative impact after exposure to haptens. Aim of the work was to assess immunologic reactivity in subjects bearing increased blood vanadium (hapten) level by using flow cytometry. There were examined adults bearing various blood vanadium concedntration. The test group was comprised by adult subjects (n = 50) having blood vanadium concentration exceeding that one for the upper limit of the reference level and mean reference group (n = 42) corresponding to reference range by 3.7- (р 0.001) and 4.3-fold, respectrively, It was found that subjects with excessively vanadium-contaminated serum were featured with stronger lymphocytes activation, increased count of effector helper T cells, lowered count of regulatory lymphocytes and decreased humoral immune arm, and suppressed p53-dependent control of cellular cycle. Thus, flow cytometry allows to assessing immunologic reactivity in subjects with varying level of blood exogenous chemicals as well as determining body adaptation potential to ewffects exerted by environmental chemical cues.
Immunoregulatory effects of flavonoid-containing medicinal herbs in human peripheral blood mononuclear cells
Authors: Mikhailova I. V. , Perunova N. B. , Ivanova E. V. , Chaynikova I. N. , Filippova Yu. V. , Kuzmicheva N. A.
Published: April 2022

Plant-derived medicinal products provide a prominent advantage due to their low toxicity to humans and combined effects of biologically active substances, mainly presented by polysaccharides, flavonoids and terpenoids. One of the mechanisms undedrlying effects from medicinal plants on the immunoregulationrelated events is mediated via controlled production of certain cytokines. Here we examined immunoregulatory activity of water extracts derived from medicinal plant raw materials (LRS) containing polyphenolic compounds – flavonoids (rutin, quercetin, called P-vitamins). The aim of the study was to assess profile and level of cytokines secreted by human peripheral blood mononuclear cedlls exposured to flavonoid-containing LRS water extracts. LRS (1:10) water extracts of the following species were used: black currant leaves (Ribes nigrum L.), field horsetail grass (Equisetum arvense L.), common yarrow grass (Achillea millefolium L.), licorice roots (Glycyrrhiza uralensis Fisch.), sand immortelle flowers (Helichrysum arenarium (L.) Moench), wild strawberry leaves (Fragaria vesca L.), fruit common bird cherry (Padus avium Mill.), tansy flowers (Tanacetum vulgare L.) and oat grass (Avena sativa L.) (all purchased at the pharmacy). Production of pro – (TNFα, IL-8, IL-1β) and anti-inflammatory (IL-10) cytokines was measured by using ELISA kits (“Cytokine”, Russia) in mononuclear cell culture supernatant treated with / without LRS (experiment and control group, respectively). Amount of flavonoids contained in flowers and leaves was quantified aftedr complexation reaction with aluminum chloride on UV-3600 spectrophotometer (Shimadzu, Japan). It was found that LRS water extracts predominantly inhibited production both of pro- (TNFα, IL-8, IL-1β) and anti-inflammatory (IL-10) cytokines so that magnitude of such suppressive effect ranged from 51.5±3.4 to 99.5±4.1% compared to untreated control samples (p 0.05). Total flavonoid level in the LRS samples diirectly correlated with intensity of related immunoregulatory activity on cytokine secretion particularly TNFα (r = 0.65), IL-8 (r = 0.4), IL-1β (r = 0.48) and IL-10 (r = 0.68). The data of our study allow to conclude that extracts from the examined medicinal plant raw materials can be considered as promising components while developing new drugs with exhibiting immunoregulatory and antiflogogenic effects.
Chronic immune activation reduces CD4+T cell susceptibility to IL-7 in HIV-infected patients that poorly respond to antiretroviral therapy
Authors: Saidakova E. V. , Korolevskaya L. B. , Shmagel K. V.
Published: April 2022

Approximately 30 % of HIV-infected patients with viral load being suppressed during the course of antiretroviral therapy do not recover their peripheral CD4+T-lymphocyte counts. The reason for this phenomenon, named immunological non-response to treatment, remains unknown. In HIV-positive subjects receiving treatment, interleukin 7 plays a key role in increasing the number and supporting the viability of CD4+T-lymphocytes. We hypothesized that chronic immune activation, which develops in response to immunological failure during the therapy course, may reduce the susceptibility of CD4+T-cells to interleukin 7 in HIV-positive subjects. We examined 38 HIV-infected immunological non-responders to therapy; 42 HIVpositive patients with a standard response to treatment; 19 uninfected volunteers. The content of CD4+, CD4+CD127+ and activated HLA-DR+CD38+T-lymphocytes was determined in the peripheral blood of the examined individuals; the concentration of interleukin 7 was established. As a result, it was shown that interleukin 7 concentrations in the blood plasma of HIV positive immunological non-responders to treatment does not differ from the corresponding values of patients who gave a standard response to antiretroviral therapy. At the same time, immunological non-responders to treatment compared with subjects of both control groups were characterized by a deficiency of absolute and relative CD4+CD127+T-cell counts capable of responding to interleukin 7. Moreover, the interleukin 7 receptor expression level was reduced on CD4+T-lymphocytes of immunological non-responders. The higher was the frequency of activated CD4+T-lymphocytes; the lower was the CD127+ expression density. It should be noted that after excluding the data obtained from patients coinfected with HIV and hepatitis C virus, which are known to have significantly higher levels of chronic immune activation and systemic inflammation, we found no differences in CD127 expression between HIVpositive patients with distinct effectiveness of the immunological response to treatment. Thus, in the present study, we showed that in HIV-infection, poor immunologic response to antiretroviral therapy is associated with a decrease in the CD4+CD127+T-cell counts. Moreover, an increase in the level of chronic immune activation is associated with a decrease in CD127 expression density on CD4+T-lymphocytes.
Effect of ultrasonic cavitation on pro-inflammatory cytokine profile in complex therapy of patients with acute rhinosinusitis and exacerbation of chronic suppurative otitis media
Authors: Korkmazov M. Yu. , Korkmazov A. M. , Dubinets I. D. , Smirnov A. A. , Kornova N. V.
Published: April 2022

Patients with exacerbated chronic suppurative otitis media occurring in subjects with acute rhinosinusitis often consulted by ENT spacialists. A literature review has shown that much attention is paid to improving conservative therapy for such patients, and non-drug techniques remain applied rarely. In this context, based on a detailed study of biophysical characteristics, an opportunity of using low-frequency ultrasonic cavitation in combination therapy to increase local immunological resistance of mucous membranes in ENT organ cavities is justified. The aim of the study was to increase clinical therapeutic effectiveness of acute rhinosinusitis and exacerbated chronic suppurative otitis media based on examining timeframe necessary for normalization of pro-inflammatory cytokine profile after using low-frequency ultrasonic cavitation in combination therapy. 63 patients were enrolled to the study. The control group (n = 15) consisted of healthy volunteers, whereas main group had 48 patients with acute rhinosinusitis and exacerbated chronic suppurative otitis media, subdivided into 2 subgroups: subgroup 1 (n = 20) – patients receiving conventional treatment methods (elimination, unloading, local and systemic antibacterial therapy, puncture and anti-inflammatory treatment), subgroup 2 (n = 28) – patients underwent low-frequency ultrasonic cavitation (frequency 29 kHz, amplitude 25 μm) in combination therapy. Washouts from the surface mucous membranes of nasal cavity and nasopharynx were examined for level of IL-1β, IL-2, IL-8, IL-10, TNFα, IFNγ levels before treatment, at day 2, 7, 10 days and in one month after treatment. Application of low-frequency ultrasonic cavitation in combination therapy in patients with acute rhinosinusitis associated with exacerbated chronic suppurative otitis media is accompanied by early recovery of balance in pro-inflammatory cytokines comparewd with conventional treatment methods. Data analysis showed that positive and satisfactory treatment result was achieved in 11 (56.2%) and 22 (78.2%) as well as 7 (36.2%) and 6 (21.8%) patients from subgroup 1 and 2, respectively. In two patients from subgroup 1 the result was noted as unsatisfactory. Early recovery in balance of pro-inflammatory cytokines, improvement of clinical results and shortened treatment duration were observed after using low-frequency ultrasonic cavitation in combination therapy of patients with acute rhinosinusitis and exacerbated chronic purulent otitis. The data obtained may serve to justify introduction of low-frequency ultrasonic cavitation into combination conservative therapy of infected nasal and middle ear cavities as an effective and non-invasive approach.
PGC-1α in human CD4+T cell subsets
Authors: Vlasova V. V. , Shmagel N. G.
Published: April 2022

CD4+T lymphocyte pool is heterogeneous in nature consisting of distinct subsets. The functional activity of each subset is highly influenced by how its energy metabolism is controlled. In naïve, central memory, effector memory, and TEMRA CD4+T cells received from healthy volunteers aged 29-42 years we evaluated the level of the major cell energy metabolism regulator: transcriptional coactivator PGC-1α. PGC-1α was shown to be expressed in all CD4+T cells. Its level in central memory, effector memory, and TEMRA cells was higher than that in naïve cells for both conventional and regulatory CD4+T lymphocytes. Moreover, its level was found to be higher in conventional when compared with regulatory CD4+T cells. Our findings suggest that regulatory and conventional CD4+T cells rely on PGC-1α to a different extent. Apparently, PGC-1α is an important but not the only factor influencing the functional state of mitochondria in regulatory CD4+T lymphocytes.
Assessing physical development and immunological parameters in adolescent girls with altered menstrual cycle
Authors: Komleva M. O. , Smolyagin A. I. , Konstantinova O. D. , Komleva N. V.
Published: April 2022

Gynecological morbidity particularly formation of menstrual function poses an important task because menstrual irregularities comprise a lead pathology among adolescent girls and considered as a marker of adverse environmental impact on female body [1, 2, 3]. The territories of the Orenburg Region [4] are known to be coupled to profound environmental and hygienic issues. We acknowledge the influence of anthropogenic stress on physical development and health in childhood by recording deviated physical development most frequently in children living in ecologically unfavorable territories [5]. Previously, we published the data on gynecological morbidity pattern in adolescent girls living in the Orenburg Region in territories with differed 7 year-monitored (from 2010 to 2016) anthropogenic stress [6]. Here we present the data on surveying girls aged 15-17 years with menstrual irregularities (MIs) living in the regions of the Orenburg region with varying anthropogenic stress assessed for their physical development, hormonal and immunological parameters. 2010- 2019 primary gynecological morbidity data were assessed based on available annual reports for various territories of the Orenburg Region. Subjects residing in the Western, Central and Eastern territories of the Orenburg Region were assesed based immune status data such as parameters of cell-mediated immunity, phagocytic indices, serum immunoglobulin class A, M, G as well as circulating immune complex levels. Hormone status was analyzed by assessing serum level of thyroid and sex hormones. It was found that oligomenorrhea in MIs was prevalent that tended to result in leptosomy and pachisomy in physical development. Most changes in adolescent girls were found in relative frequency of peripheral blood CD3+, CD4+ and CD19+ lymphocytes, phagocytic index as well as IgM, estradiol, progesterone, testosterone levels, LH, 17-OH-progesterone and cortisol. Our study demonstrated that adolescent girls living in the West and East of the region were featured with dominant oligomenorrhea in MIs associated with physical development tended to leptosomy and pachisomy. Assessing parameters of physical development in adolescent girls is of great importance and should be performed to diagnose potential menstrual irregularities. Thus, our data underline importance of negative impact of anthropogenic burden on gynecological health in adolescent girls.
Evaluating T and B cell lineage differentiation stage and related prognostic impact in miscarriage
Authors: Baturina I. L. , Loginova Yu. V. , Nikushkina K. V. , Emelyanov I. V. , Zotova M. A. , Nikonova T. I.
Published: April 2022

The WHO (World Health Organization) defines miscarriage as two or more pregnancies documented in woman medical history ended up with spontaneous miscarriage at stage of up to 22 weeks of pregnancy from conception. Habitual miscarriage of pregnancy (HMP) is one of high priority problems for infertile marriages comprising 5-20% among other causes of miscarriage. As many as 80% of all idiopathic HMP cases are associated with immune-related disorders. Currently, many researchers have being paying more attention to examining effects of T and B cells at varying differentiation stage in developing immune response against allogenic graft and formation immunological tolerance. However, it is worth noting that pregnancy-associated human hormone chorionic gonadotropin (HCG) exhibits a marked immunosuppressive effect by regulating regulatory T (Treg) cell functional activity. It has been proven that HCG contributes to increasing Tregs level in periphery and recruiting them to the embryo implantation zone, thus establishing immunological tolerance during pregnancy. However, no data regarding HCG effects on T and B cells at various differentiation stage were obtained during HMP. A correlation analysis between frequency of T and B cells at various differentiation stage and level of serum HCG in women with HMP was performed. It was found that low level HCG was associated with decreased naive T and B cell frequency paralleled with elevated percentage of effector memory CD8+ (Tem) that may serve as a poor prognostic sign especially in early stage of pregnancy.