Lymphocyte Concentrations Research Articles

Гістоструктура великого чепця людини в нормі і перитоніті

The purpose of the work was to study the histological structure of the greater omentum in the people of second mature and elderly age in normal condition and in peritonitis. Materials and methods. The materials of the study were 40 greater omenta of deceased people (20 males and 20 females) of the second mature and elderly age without pathology in the abdominal cavity and 10 greater omenta of deceased people from peritonitis taken in accordance with the cooperation agreement. Pieces of greater omenta were fixed with a 10% solution of neutral formalin. Paraffin blocks were made according to the traditional method, followed by making sections that were stained with hematoxylin and eosin. Histological specimens were studied using a light microscope "MICROmed" XS-3320 in transmitted light using an increase of ×40, ×100, ×400 with the photographing of micropreparations on the camera Ningero Sheng Heng Optics and Electronics Co. Results and discussion. The findings of the study showed that the histological structure of the tissue of the greater omentum in women and men of these ages has common structural features. Histological sections stained with hematoxylin and eosin revealed that normally the outside of the greater omentum is covered with a solid layer of mesotheliocytes, located on the basal plate, deeper there were “milk spots”, white adipocytes, which formed individual fat particles, separated by connective tissue fibers. “Milk spots” do not have capsules, in contrast to lymph nodes, and contain lymphocytes and macrophages that emerge from their fenestrated postcapillary venules and migrate into the abdominal cavity through “stigmas”. Normally, active and inactive “milk spots” are present in the greater omentum in adults. “Milk spots” had an oval, irregular and spherical shape and different sizes. In the thickness of the tissue of the greater omentum there were lymph nodes, which, in contrast to the "milk spots" on the outside were covered with a connective tissue capsule. In the thickness of the nodule, trabeculae extend from the capsule. Marginal and medullary sinuses were determined. Lymphocytes were the main cellular component of lymph nodes. Conclusion. In peritonitis, disruption of the continuous mesothelial cover of the greater omentum, resulted from disintegration of mesothelial cells; some areas of their adhesion and desquamation were observed. Areas with inflammatory infiltration, plethora of arterial and venous microvessels and an increase in active “milk spots” with a high content of lymphocytes were found in the fat particles of the greater omentum

The association between blood lymphocyte NMDAR, group I mGluRs and cognitive function changes in occupationally aluminum-exposed workers and verification in rats

BackgroundMany studies have shown that occupational aluminum (Al) exposure could affect the cognitive functions of workers and cause mild cognitive impairment (MCI). Glutamate receptors (GluRs) play an important role in learning and memory functions. Methods352 workers in a large Al production enterprise were investigated in this research. MMSE, CDT, DST, VFT, FOM were used to evaluate the cognitive functions of workers. Plasma Al levels as exposure indices were measured by Graphite Furnace Atomic Absorption Method (GFAAS). The expression of GluRs was measured by ELISA. Cognitive function comprehensive scores were obtained through factor analysis. Then a rat model of chronic AlCl3 exposure was established. The detection method of Al levels and protein expression were the same as mentioned-above. ResultsCompared with the Q1 group, the DST, VFT, and comprehensive cognitive function scores of the Q4 group were lower(P < 0.05). For every 1μg/L increase in plasma Al concentration, the risk of cognitive impairment increases 1.051 times (95 %CI:1.031,1.072). Both NMDAR1 and NMDAR2A protein expression level of Q1 group were higher than those of Q2, Q3, Q4 group (all P < 0.05). The mediating effect ratio of NMDAR1 between plasma Al levels and cognitive function comprehensive scores was a1*b1/c=11.30 %, and the mediating effect ratio of NMDAR2A was |a2*b2/c|=21.77 %. Compared with control group, the escape latency of rats in the high Al dose group was longer day by day (P < 0.05). With the increase of Al dose, the relative expression of NMDAR1, NMDAR2A, NMDAR2B, GluR1 and mGluR5 in cerebral cortex and lymphocytes of rats were decreased (P < 0.05). The result of correlation analysis on NMDAR1 protein expression between brain cortex and lymphocyte showed that the correlation coefficient is r = 0.646(P < 0.05). ConclusionTaking together the results from both Al exposed workers and animal, there is a certain correlation between NMDAR1 protein contents of brain cortex and peripheral lymphocytes. We propose that lymphocyte NMDAR1 could be considered as a peripheral potential marker of cognitive impairment for further observation.

PSXVI-15 Study of the content of maternal lymphocytes with Barr’s bodies in the bloodstream and red bone marrow of newborn male mice

Abstract In animals with hemochorical placenta, the transfer of maternal antibodies and white blood cells to the fetus can take place along the transplacentary pathway. In the first hours of life, the intestines of newborn animals are able to absorb antibodies from colossus by pinocytosis. Similarly, maternal lymphocytes can get into the blood of a newborn. The aim of this work was to identify maternal lymphoid cells with sexual x-chromatin in the blood and red bone marrow of newborn male mice. Studies were conducted on nonlinean lactating mice and newborn male mice. Two groups of five animals were formed. The mice had breast glands. A longitudinal incision was made and a print smear was prepared. The bone marrow was taken from the proximal part of the femur. Blood was obtained by amputating the tip of the tail. All the drugs were stained by Pappenheim and examined with immersion optics. In the study of breast tissue smears, the number of lymphocytes in the microscope fields was counted. Visualization of drugs showed their high frequency of occurrence (15,1±1.7 in 100 fields of vision). In three-day male mice, the percentage of lymphocytes in the blood was 55.4±3.5%, including cells with x-chromatin (2.4±0.2±%). of which 5.3±3.2% were maternal cells with Barra Taurus. The appearance of maternal lymphocytes in the systemic circulation of newborn male mice is explained by the possibility of their transfer through the hemochorial placenta or absorption into colos dairy through the intestines. Active migration of maternal lymphocytes from the systemic circulation of young animals to the red bone marrow is necessary for the formation of cellular immunity in the body during the period of growth and development.

Clinical and immunological characteristic and dynamic of the secondary diseases stage of HIV infection in children, taking into account the route of infection

The purpose is to characterize the clinical picture, immune status and the natural history of HIV infection in the stage of secondary diseases in vertical and parenteral infected children.Materials and methods. A clinical, laboratory, instrumental, immunological examination of 132 children in the stage of secondary diseases infected with HIV in a vertical way (90; I group) and parenteral way in infancy (42; II group) was carried. Results. The clinical picture of HIV infection in the stage of secondary diseases included various combinations of HIV-associated symptoms, opportunistic infections, tumors, which determines the symptomatology of a particular stage. The use of the Cox regression mathematical model of proportional intensities demonstrated a reduction in the duration of stage 4A (RR 5.8; 95% CI 1.4—10.5; P &lt; 0.001), 4B (RR 3.4; 95% CI 1.8—4.3; P &lt; 0.001) and 4V (RR 4.8; 95% CI 1.2—8.9; P &lt; 0.001) in children of group I. Using the method of multiplying Kaplan-Meier estimates, the significant differences between the time curves from the beginning of the 4A stage (Р = 0.044), 4B (P &lt; 0.001) and 4V (Р = 0.029) before the transition to the subsequent stage in children of groups I and II were established. The content of CD4 lymphocytes in the blood in patients of group I was higher as compared with group II at the time of debut of stages 4A (Me 37.5%, IQI 33—40% and Me 22%, IQI 18—24%; Р &lt; 0.001), 4B (Me 25%, IQI 22—28% and Me 20%, IQI 18—22%; Р &lt; 0.001) and 4V (Me 14%, IQI 12—18% and Me 11%, IQI 10—14%; Р = 0.047).Conclusion. HIV infection in the stage of secondary diseases in children infected with the vertical way is characterized by more rapid progression compared with parenteral infected in infancy patients, which is associated with the immaturity of the immune system.

Assessment of bovine respiratory disease progression in calves challenged with bovine herpesvirus 1 and Mannheimia haemolytica using point-of-care and laboratory-based blood leukocyte differential assays.

Blood leukocyte differentials can be useful for understanding changes associated with bovine respiratory disease (BRD) progression. By improving turnaround time, point-of-care leukocyte differential assays (PCLD) may provide logistical advantages to laboratory-based assays. Our objective was to assess BRD progression in steers challenged with bovine herpesvirus 1 and Mannheimia haemolytica using point-of-care and laboratory-based blood leukocyte differentials. Thirty Holstein steers (average body weight of 211 kg + 2.4 kg) were inoculated intranasally on day 0 with bovine herpesvirus 1 and intrabronchially on day 6 with Mannheimia haemolytica. Blood leukocytes differentials were measured using both assays from study days 0 to 13. Linear mixed models were fitted to evaluate the associations between: (1) the type of assay (laboratory-based or PCLD) with respect to leukocyte, lymphocyte, and neutrophil concentrations; (2) study day with cell concentrations; and (3) cell concentrations with lung consolidation measured at necropsy. Point-of-care leukocyte, lymphocyte, and neutrophil concentrations were significantly associated (P < 0.05) with the respective cell concentrations obtained from the laboratory-based leukocyte differential. Cell concentrations reported by both assays differed significantly (P < 0.05) over time, indicating shifts from healthy to viral and bacterial disease states. Lymphocyte concentrations, lymphocyte/neutrophil ratios obtained from both assays, and band neutrophil concentrations from the laboratory-based assay were significantly associated (P < 0.05) with lung consolidation, enhancing assessments of disease severity. The PCLD may be a useful alternative to assess BRD progression when laboratory-based leukocyte differentials are impractical.

Interleukin-30 feeds breast cancer stem cells via CXCL10 and IL23 autocrine loops and shapes immune contexture and host outcome

BackgroundBreast cancer (BC) progression to metastatic disease is the leading cause of death in women worldwide. Metastasis is driven by cancer stem cells (CSCs) and signals from their microenvironment. Interleukin...

Prevalence of carbohydrate metabolism disorders in patients with new coronavirus infection

BACKGRAUND: There is evidence of a multifactorial effect of SARS-CoV2 on carbohydrate metabolism with the development of hyperglycemia and the weighting of COVID19 even in people without DM.AIMS: Assess the prevalence of disorders carbohydrate metabolism (DCM) in hospitalized patients with a new coronavirus infection without a history of DM.MATERIALS AND METHODS: Patients with PCR-confirmed diagnosis of COVID19 aged 18-75 years (n=72) without a history of diabetes were examined. Observation was carried out from the moment of hospitalization to discharge. Patients were collected anamnesis data, laboratory and instrumental studies, HbA1c, fasting plasma glucose (FPG), postprandial glycemia.RESULTS: The prevalence of DCM (HbA1c≥6%) in 72 patients with COVID19 without a history of diabetes admitted to the hospital was 41,7%, while HbA1c ≥6,5% had 8,3%. The median HbA1c in the moderate-flow group was 5,7% [5,3–6,0], and in the severe-flow group it was 6,0% [5,8–6,2] (p=0,008). Participants were divided into groups according to the level of HbA1c≥6% and &lt; 6%. The examined patients showed a high prevalence of risk factors for developing DM: age over 45 years — 83,3%, cardiovascular diseases — 46,3%, obesity — 50%. The study groups didn’t differ statistically in terms of risk factors for DM. In the group with HbA1c≥6%, FPG≥6,1 mmol / l on the second day and postprandial glycemia ≥7,8 mmol/l were observed in more cases than in the group with HbA1c&lt;6% (39,1% vs 12,9%, p=0,051 and 47,8% vs 3,2%, p=0,0001, respectively). The prevalence of DCM in HbA1c was higher than in FPG (41,7% vs 29,2%, p=0,006). On the seventh day, the number of patients with FPG ≥ 6,1 mmol / l in the first group decreased from 39,1% to 4,4% (p=0,01), and in the second group-from 12,9% to 9,7% (p=1,0). There was a direct correlation between the level of HbA1c and C-reactive protein (r=0,271; p=0,048), and an inverse correlation with the content of lymphocytes in the blood (r=-0,25; p=0,068).CONCLUSIONS: In patients with a new coronavirus infection without a history of DM, a high prevalence of DCM was detected — 41,7%. Against the background of comparability of the studied groups by risk factors for DM, an increase in HbA1c, FPG and postprandial glycemia is a manifestation of transient hyperglycemia. Given the high prevalence of DCM, it can be assumed that SARS-CoV2 has diabetogenic properties.

Electrical Conductivity of Bone Marrow Cell Cultures and Their Connection with Proliferative Activity: Age Aspect

Functional activity is a basic concept of biology; however, instrumental methods of its determination are absent. The interrelation between bone marrow cell proliferative activity, as one of the functional activity parameters, the content of calcium, copper, and reactive oxygen species (ROS) in the cells, and the electrical conductivity of the cell culture was studied in young and old Wistar rats aged 3 and 20 months. We determined the electrical conductivity of the bone marrow cell cultures and parameters of bone marrow cells (proliferative activity and calcium, copper and ROS content). The bone marrow cells of old intact animals had higher proliferative activity in the primary culture as compared to that of young animals. The content of the 8 main morphological cell types in the young and old animals were similar, while the lymphocyte content was larger in the old animals. Content of ions in the bone marrow cell cultures of old animals as compared with that in young animals varied as follows: Content of calcium was 75 % higher, copper was 5 times lower, and ROS was 2.5 times lower. It was found that the conductivities of the pure culture medium and of that after the cultivation of the bone marrow cells in the nutrient medium were significantly different. It has been suggested that the electrical conductivity of biological media could be used as an integral characteristic of the ionic composition and structural organization of biological media. HIGHLIGHTS Electrical conductivity of bone marrow cells suspension of young animals was decrease to compared with this indicator of old animals Proliferative activity is correlated with electrical conductivity Electrical conductivity of biological media is influenced both the composition, and macromolecules and their state of aggregation

Immunomodulating Therapies in Breast Cancer-From Prognosis to Clinical Practice.

Simple SummaryThe role of the immune system in breast cancer has been debated for decades. It is generally accepted that tumor-infiltrating lymphocytes are associated with positive prognostic and predictive effects, especially in triple negative breast cancer. This subset of breast cancer is characterized by the absence of hormone receptors and human epidermal growth factor receptor 2. Compared to other breast cancer subtypes, triple-negative breast cancer has more mutations and neoantigens, making it more immunogenic. Releasing the brakes on the immune system with the help of so-called immune checkpoint inhibitors leads to activation of the immune system and destruction of cancer cells. This, in turn, improves survival, especially in early and advanced triple-negative breast cancer. A new and promising strategy is the enhancement of the immune response using individualized mRNA vaccines against tumor-specific neoantigens.The role of the immune system in breast cancer has been debated for decades. The advent of technologies such as next generation sequencing (NGS) has elucidated the crucial interplay between somatic mutations in tumors leading to neoantigens and immune responses with increased tumor-infiltrating lymphocytes and improved prognosis of breast cancer patients. In particular, triple-negative breast cancer (TNBC) has a higher mutational burden compared to other breast cancer subtypes. In addition, higher levels of tumor-associated antigens suggest that immunotherapies are a promising treatment option, specifically for TNBC. Indeed, higher concentrations of tumor-infiltrating lymphocytes are associated with better prognosis and response to chemotherapy in TNBC. An important target within the cancer immune cell cycle is the “immune checkpoint”. Immune checkpoint inhibitors (ICPis) block the interaction of certain cell surface proteins that act as “brakes” on immune responses. Recent studies have shown that ICPis improve survival in both early and advanced TNBC. However, this comes at the price of increased toxicity, particularly immune-mediated toxicity. As an alternative approach, individualized mRNA vaccination strategies against tumor-associated neoantigens represent another promising approach leading to neoantigen-specific immune responses. These novel strategies should help to improve treatment outcomes, especially for patients with triple negative breast cancer.

Порівняльний аналіз показників системи імунітету у хворих на інфекційні хвороби системи дихання

У статті наведені дані про актуальність гострих респіраторних захворювань, пневмоній у військовослужбовців. Подані результати вивчення стану імунної системи у військовослужбовців під час проведення АТО, пацієнтів із гострими респіраторними захворюваннями й атиповою пневмонією. Дослідження показали, що в пацієнтів з атиповою пневмонією порівняно з пацієнтами з гострими респіраторними захворюваннями в перші дні захворювання реєструється більш значний вміст лейкоцитів за рахунок нейтрофілоцитів, серед яких збільшується вміст молодих клітин (метамієлоцити та стрижнево-ядерні нейтрофілоцити). У 100 % пацієнтів спостерігається збій імунної системи за вмістом молодих та атипових лімфоцитів. Отримані результати можуть бути використані як додатковий критерій диференціальної діагностики гострих респіраторних захворювань та атипової пневмонії в перші дні захворювання.

The effect of photodynamic therapy on the hematological and biochemical parameters of the blood of cats

Relevance. In this article, we present experimental study on the effect of photodynamic therapy with a chlorin-type photosensitizer on the hematological and biochemical blood parameters of cats with malignant oncological diseases.Methods. During conducting studies in experimental animals, we took blood samples from 44 cats aged 8 to 16 years, of different breeds and different sexes, before photodynamic therapy and two days after treatment, in order to determine the possible effect of therapy on the blood counts of patients. Blood sampling was carried out according to the standard method. Hematological examination was performed on a PCE90vet analyzer (HTI, USA), biochemical on an automatic biochemical analyzer Biosystems A15 (Biosystems, Spain) and on a semi-automatic analyzer Biohaem SA (HTI, USA). Photodynamic therapy was performed according to the standard method, with the preliminary introduction of the photosensitizer “Photoditazine” at a dose of 0.8– 1 mg/kg, 3 hours before irradiation.Results. The most significant changes in the hematological study were found among the following parameters: the level of white blood cells after irradiation increased by 18%, the number of eosinophils decreased by 28%, the number of segmented neutrophils increased by 11%, the content of lymphocytes decreased by 21%. When studying the biochemical parameters of blood, changes were found in the following parameter: the glucose level increased by 13% after irradiation, the level of GGT decreased by 19% after irradiation. At the same time, all indicators of the hematological and biochemical composition of the blood were within the normal values for this type of animal. Photodynamic therapy does not significantly affect the hematological and biochemical parameters of the blood of cats, this proves the safety of using this method of treatment in these animals.

Effect of dietary phytobiotic mixture on growth performance, nutrient utilization, and immunity in weaned piglets

This study investigated the effects of dietary phytobiotic mixture on growth performance, blood profiles, immune response, and fecal microorganisms in weaned piglets. Twenty four weaned crossbred piglets were equally divided into four groups in a completely randomized design. The animals in 4 groups were fed a basal diet added with (1) no antibiotics and phytobiotics (CON), (2) bacitracin (0.5g/kg; AB), (3) a blend of Cinnamomum zeylanicum and Trachyspermum copticum essential oils (0.3g/kg and 0.4g/kg, respectively; EO), and (4) plant extracts (PEO) of Mikania micrantha and Garcinia lanceifolia (2.8g/kg and 1.4g/kg, respectively) and C. zeylanicum and T. copticum essential oils (0.3g/kg and 0.4g/kg, respectively). Inclusion of AB, EO, and PEO did not affect final body weight, average daily gain, feed intake, feed efficiency, and nutrient digestibility. Compared with the CON, serum protein profiles were not affected, but a few lipid profiles were improved, particularly cholesterol, low-density lipoprotein, and high-density lipoprotein in the EO and PEO groups. Lymphocyte proliferation index and concentrations of IgG and IgA and TNF-α were not affected by any treatments. The concentrations of IgM increased (P = 0.04) at 28days and tended to increase (P = 0.10) at 56days in the EO group. Serum IL-1β levels decreased on days 28 and 56 in the EO and PEO groups. Fecal Lactobacilli population generally increased (P < 0.01) in the AB, EO, and PEO groups compared with the CON. Fecal enterobacterial numbers were always greater for AB than for CON, EO, or PEO, but enterobacterial populations were sometimes lower in the EO group than the CON group. In conclusion, dietary EO or PEO has no effect on the growth performance, but it may improve a few lipid profiles, immune responses, and fecal microbial populations in piglets.

ASSOCIATIONS BETWEEN BLOOD CONCENTRATIONS OF CYTOTOXIC CD8+ CELLS AND LYMPHOCYTE APOPTOSIS IN HEALTHY HUMANS

Introduction: Cytotoxic T-lymphocytes play an important role in a specific immune response via a lytic effect in relation to abnormal cells. The number of these cells greatly increases sin pathological states. In addition, an increased cytotoxic activity is a characteristic of the immune response of people living in the Far NorthTherefore, it is important to understand what function cytotoxic T-lymphocytes predominantly perform in healthy people in the North - cytolytic or suppressor? Aim: To assess associations between CD8+ concentration and immune response and apoptotic deaths of the lymphocytes in healthy individuals. Methods: Ninety-three healthy adult residents of the Russian North comprised the sample. Apoptotic lymphocyte death was studied by flow cytometry. FITC-annexine-V and propidium iodide labelled cells were detected. Concentrations of cytokines and apoptosis mediators were assessed by a solid-phase enzyme immunoassay. Neutrophiles, monocytes and phagocytic activity of neutrophils were studied in blood smears stained by Romanowsky's - Giemsa. The level of phenotypic activity of lymphocytes was assessed by double peroxidase labeling using monoclonal antibodies. The data were presented using means, standard deviations, medians, the 1st and the 3rd quartiles. All study participants were divided into two groups: with normal- (0.2-0,4 х109 kl/l) and elevated (more 0,6 х109 kl/l) blood cytotoxic lymphocyte levels. The groups were similar in terms of by age- and gender distribution. Continuous variables were analyzed using Mann-Whitney tests. Results: In individuals with an increased level of cytotoxic CD8+ lymphocytes in peripheral venous blood had greater concentrations of leukocytes (7.4 ± 0.49 х109 cells/l vs. 5.5 ± 0.23 х109, p = 0.003), lymphocytes (2.8 ± 0.17 х109 cells/l vs.1.8 ± 0.07 х109 cells/t p = 0.005), and mature neutrophils (4.1 ± 0.19 х109 cells/l vs. 3.4 ± 0.49 х109 cells/l, p = 0.013). No associations between the level of apoptosis of lymphocytes (AnV+/PI-) and concentrations of sFasL, TRAIL, TNFa, and cytochrome C were observed. Conclusions: Lymphocytes CD8+ in healthy residents of the Russian North perform mainly cytotoxic function, which is not related to apoptotic cellular death.

The effect of the content of ApoA-I in peripheral blood on the state of immune homeostasis in people living in extreme climatic conditions of the Arctic.

The paper presents data on the impacts of the content of ApoA-I in peripheral blood on the state of immune homeostasis in people living in extreme climatic conditions of the Arctic. From the village of Revda, Murmansk region, 191 people were examined, 160 women and 31 men, aged from 21 to 55 years. The analysis of the results was carried out depending on the level of ApoA-I content: 111 examined people had a low content of ApoA-I (< 115 mg/dl) and 80 people had a concentration of ApoA-I - within the physiological norm (115-220 mg/dl). Deficiency of ApoA-I is associated with an increase in plasma concentrations of total cholesterol in 37.5% and triglycerides in 62.5% of cases. Low content of ApoA-I is associated with a decrease in the content of neutrophilic granulocytes and an increase in the concentration of small lymphocytes, IL-10 and IgE. Deficiency of ApoA-I is associated with an increase in the content of CD45RA+, CD16+, CD56+ lymphocyte phenotypes in blood. Low concentrations of ApoA-I are associated with low expression activity of L-selectin gene and free L-selectin ligand. Due to deficiency of ApoA-I, no significant differences were detected in the content of transferrin, free transferrin receptor, haptoglobin, free calcium-dependent cell adhesion protein, and free pool of receptors involved in apoptosis. Conclusion: deficiency of ApoA-I in blood plasma is associated with increased migration of neutrophils into the tissue and cell-mediated cytotoxicity of lymphocytes and occurs because of the effect of decreased activity of the level of antioxidant defense, changes in the structure of cell membranes and the participation of adhesion molecules.

Analysis of eosinophil and lymphocyte concentrations on the incidence of mild and severe acute asthma exacerbations

Introduction: Exacerbation of asthma is an episode characterized by an increase in symptoms of progressive shortness of breath, coughing, wheezing, chest tightness, and a progressive decrease in lung function. Among the cells involved and activated in acute exacerbations in asthma are eosinophils and lymphocytes.

Особенности использования лимфоцитарного теста для прогнозирования степени тяжести острого лучевого поражения

One of the methods of biological dosimetry is the use of information on the concentration of lymphocytes in the peripheral blood of victims in the first days after irradiation. The aim of the study was to validate the lymphocyte test method for predicting the severity of acute radiation injury, taking into account the dose rate factor. Materials and research methods. The method of investigation was a correlational analysis of clinical, dosimetric and laboratory data of the victims of the accident at the Chernobyl nuclear power plant in 1986 (n=65) and in radiation accidents with gamma-neutron irradiation (n=19). The data were taken from the database of acute radiation injuries in humans of A.I. Burnazyan Federal Medical Biophysical Center of the Federal Medical and Biological Agency of Russia. Results of the study and their analysis. The results of correlation analysis indicated that average lymphocyte concentration in the range of 0.4-0.8×109/l on day 3-6 post-irradiation with dose rates greater than 2 Gy/h resulted in an average dose estimate which was 40.0% higher than that for dose rates of less than 2 Gy/h. Absolute error of dose estimation is (±1.0-1.5) Gy. For lymphocyte concentrations higher than 0.8×109/l the prognosis is uncertain: the range of dose assessment variability is 1-4 Gy. At a lymphocyte concentration of less than 0.4×109/l the average dose estimate is more than 4.0 Gy, corresponding to a severe or extremely severe degree of acute radiation disease. The predicted degree of severity of radiation injuries in the presence of the neutron component of radiation is lower in comparison with the predictions based on the data on the victims of the Chernobyl accident. It is concluded that the identified dependencies can be used for medical triage of the victims at advanced stages of medical evacuation. For the purpose of correct routing of medical evacuation to specialized centers, it is advisable to allocate 4 treatment-evacuation groups.

Evidence of Subclinical Inflammation Relates to PAH Exposure in Overwintering Common Loons (Gavia immer)

Common Loons (Gavia immer) are migratory, piscivorous waterbirds that exhibit high wintering site fidelity. Forty-three immature loons were captured in 2013, 2015–2017, in southwest coastal Louisiana, an area moderately to heavily exposed to oil from the Deepwater Horizon oil spill of 2010. We analyzed blood from loons to examine associations between exposure to polycyclic aromatic hydrocarbons (PAH) and 25 blood analytes. Overall, 60% (26/43) of the loons had detectable concentrations of PAHs, with an average concentration of 55.3 ± 10.3 ng/g. After controlling for body weight, loons with detectable blood PAHs had higher concentrations of absolute eosinophils, lymphocytes, or monocytes compared to loons without PAH exposure. This study provides evidence of subclinical inflammation in Common Loons wintering in coastal Louisiana and identifies exposure to PAHs as a stressor, raising concern for potential impaired fitness in this population resulting from low-level exposure to PAHs.

Effects of time on differential leucocyte counts and biochemical parameters of ovariohysterectomy, gastrotomy and intestinal resection and anastomosis in Nigerian indigenous dogs

Differential leucocytes counts and some biochemical parameters could be affected over time by surgical procedures leading to kidney failure. Hence this study evaluates the effects of ovariohysterectomy (OVH), gastrotomy (GAT) and intestinal resection and anastomosis (ITR) on differential leucocyte counts and some biochemical parameters in Nigerian dogs. Twelve dogs of both sexes weighing 10.8±0.7 kg were randomly divided into three experimental groups of four each. The dogs were pre-treated with atropine sulphate (0.04 mg/kg), Xylazine (2 mg/kg) and propofol (6 mg/kg) parenterally, for induction and maintenance of anaesthesia. Pentazocine (3 mg/kg) was injected after surgery. Pre and post-surgery blood samples were obtained at 0, 2, 24, 48, 72, 96, 120 and 144 h respectively to determine differentials in leucocyte counts, electrolytes, lactate, blood urea nitrogen (BUN) and serum creatinine. Mathematical formulas were used to calculate plasma creatinine, creatinine clearance, plasma creatinine clearance, creatinine half- life, urine creatinine and urine volume. There were significant increases (p ≤ 0.05) in mean sodium, chloride and bicarbonate concentrations at 2, 24, 48, 72, 96 and 120 h post-surgery in group 1 and 2, while group 3 had significant decreases (p ≤ 0.05) in sodium, chloride and bicarbonate ions. Lactate value decreased significantly (p<0.05) in group 1, and increased in group 2 and 3 respectively.BUN increased significantly (p<0.05) in group 1,2 and 3.However, there were significant increases (p<0.05) in lymphocyte concentrations in group 1 and 3, respectively. Monocytes decreased significantly (p<0.05) after surgery. Conclusion: Xylazine and propofol anaesthetics cause hyperlactatemia which can be detrimental in surgical patients with co-morbidities.

Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer.

Simple SummaryTriple-negative breast cancer (TNBC) is associated with a poor prognosis, and the development of better therapeutic strategies is required. Herein, we investigated the role of the anti-angiogenic thrombospondin-1 (TSP1) in TNBC. TSP1 expression in tumor biopsies from TNBC patients was associated with a bad prognosis and a weak content of tumor-infiltrating lymphocytes (TILs). In the 4T1 mouse TNBC model, TSP1 knockdown reduced TGF-β activation and enhanced the content of TILs. Moreover, TSP1 knockdown decreased lung metastasis in syngeneic Balb/c immunocompetent mice but not in immunodeficient nude mice. Finally, TSP1 knockdown enhanced anti-PD-1 immunotherapy efficacy. Thus, targeting TSP1 may be considered as a putative therapeutic strategy in TNBC in combination with immunotherapy.Triple-negative breast cancer (TNBC) is notoriously aggressive with a high metastatic potential, and targeted therapies are lacking. Using transcriptomic and histologic analysis of TNBC samples, we found that a high expression of thrombospondin-1 (TSP1), a potent endogenous inhibitor of angiogenesis and an activator of latent transforming growth factor beta (TGF-β), is associated with (i) gene signatures of epithelial–mesenchymal transition and TGF-β signaling, (ii) metastasis and (iii) a reduced survival in TNBC patients. In contrast, in tumors expressing low levels of TSP1, gene signatures of interferon gamma (IFN-γ) signaling and lymphocyte activation were enriched. In TNBC biopsies, TSP1 expression inversely correlated with the CD8+ tumor-infiltrating lymphocytes (TILs) content. In the 4T1 metastatic mouse model of TNBC, TSP1 silencing did not affect primary tumor development but, strikingly, impaired metastasis in immunocompetent but not in immunodeficient nude mice. Moreover, TSP1 knockdown increased tumor vascularization and T lymphocyte infiltration and decreased TGF-β activation in immunocompetent mice. Noteworthy was the finding that TSP1 knockdown increased CD8+ TILs and their programmed cell death 1 (PD-1) expression and sensitized 4T1 tumors to anti-PD-1 therapy. TSP1 inhibition might thus represent an innovative targeted approach to impair TGF-β activation and breast cancer cell metastasis and improve lymphocyte infiltration in tumors, and immunotherapy efficacy in TNBC.

CMV Infection Is Directly Related to the Inflammatory Status in Chronic Heart Failure Patients.

High levels of inflammation play an important role in chronic heart failure (CHF). Patients with CHF have elevated levels of pro-inflammatory cytokines circulating systemically, mainly TNF and IL-6. However, there are almost no studies that relate these levels to the functional status of patients in CHF, much less to their CMV serostatus. In this study, patients with CHF (n=40; age=54.9 ± 6.3; New York Heart Association functional classification (NYHA, I-III) and healthy controls (n=40; age=53.5 ± 7.1) were analyzed. The serum concentrations of nine pro- and anti-inflammatory cytokines were measured by Luminex® xMap Technology and the basal level of mRNA expression of some immune molecules was quantified by TaqMan™ Array in CD4+ T-lymphocytes. The concentration of these cytokines in culture supernatants in response to anti-CD3 and LPS was also measured. The percentage of CD28null T-cells was determined, as well as the antibody titer against CMV. We found a higher concentration of all cytokines studied in CHF serum compared to healthy controls, as well as a direct correlation between functional status in CHF patients and levels of inflammatory cytokines. Moreover, the highest cytokine concentrations were found in patients with higher concentrations of lymphocytes lacking CD28 molecule. The cytokine production was much higher in CMV+ patients, and the production of these cytokines was found mainly in the T-lymphocytes of CMV+ patients in response to anti-CD3. Anti-CMV antibody levels were positively correlated with cytokine levels. The baseline expression of specific mRNA of the main molecules involved in the Th1 response, as well as molecules related to the CD4+CD28 null subset was higher in CMV+ patients. The cytokine concentrations are higher in CHF CMV+ patients and these concentrations are related to the production of antibodies against CMV. These high levels of cytokines are also associated with the more differentiated CD28null lymphocyte populations. All this, together with the dynamics of the pathology itself, makes CMV+ patients present a worse functional status and possibly a worse evolution of the pathology.