Decrease In Number Of Leukocytes Research Articles

Fetal CCL2 signaling mediates offspring social behavior and recapitulates effects of prenatal stress

Maternal stress during pregnancy is prevalent and associated with increased risk of neurodevelopmental disorders in the offspring. Maternal and offspring immune dysfunction has been implicated as a potential mechanism by which prenatal stress shapes offspring neurodevelopment; however, the impact of prenatal stress on the developing immune system has yet to be elucidated. Furthermore, there is evidence that the chemokine C-C motif chemokine ligand 2 (CCL2) plays a key role in mediating the behavioral sequelae of prenatal stress. Here, we use an established model of prenatal restraint stress in mice to investigate alterations in the fetal immune system, with a focus on CCL2. In the placenta, stress led to a reduction in CCL2 and Ccr2 expression with a concomitant decrease in leukocyte number. However, the fetal liver exhibited an inflammatory phenotype, with upregulation of Ccl2, Il6, and Lbp expression, along with an increase in pro-inflammatory Ly6CHi monocytes. Prenatal stress also disrupted chemokine signaling and increased the number of monocytes and microglia in the fetal brain. Furthermore, stress increased Il1b expression by fetal brain CD11b+ microglia and monocytes. Finally, intra-amniotic injections of recombinant mouse CCL2 partially recapitulated the social behavioral deficits in the adult offspring previously observed in the prenatal restraint stress model. Altogether, these data suggest that prenatal stress led to fetal inflammation, and that fetal CCL2 plays a role in shaping offspring social behavior.

Comparative study of the effect of different antimicrobial groups on chick blood leukogram

Diseases of bacterial etiology are a serious problem hindering the development of the poultry industry, causing serious economic damage to it.Herein we present the results of studies of the effect that drugs of different antimicrobial groups (ditrim and furazolidone) have on leukogram of Hisex Brown chicks. We studied blood values in 3 groups, group I received pure drinking water, group II received ditrim via drinking water at a concentration of 200 mg/L 10 consecutive days, whereas group III received furazolidone in the same manner. Blood samples were collected at Day 1, Day 3, Day 5, Day 7 and Day 9 after the drug withdrawal. We performed leukocyte count in chick blood in each group, then in blood smears we calculated the number of eosinophils, basophils, pseudoeosinophils, lymphocytes and monocytes. We also calculated percentages of separate white blood cell types in order to perform the white blood cell differential. We discovered that administration of furazolidone via drinking water causes a long-term decrease in leukocyte number while such decrease was not observed following administration of ditrim. Leukopenia was observed in chicks of group III at Day 1, Day 5 and Day 7, their values differing from the control values by 26%, 12% and 25% respectively. Besides the administration of furazolidone via drinking water caused changes in leukogram, manifesting in prolonged dynamics of pseudoeosinophil number and lymphocyte number, and also in transitory change in eosinophil number. We did not observe such effect on blood values following the administration of ditrim to the chicks of Group II, except for transitory eosinopenia at Day 9 of our experiment

3K3A-Activated Protein C Prevents Microglia Activation, Inhibits NLRP3 Inflammasome and Limits Ocular Inflammation.

3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with pleiotropic cytoprotective properties albeit without the bleeding risks. The anti-inflammatory activities of 3K3A-APC were demonstrated in multiple preclinical injury models, including various neurological disorders. We determined the ability of 3K3A-APC to inhibit ocular inflammation in a murine model of lipopolysaccharide (LPS)-induced uveitis. Leukocyte recruitment, microglia activation, NLRP3 inflammasome and IL-1β levels were assessed using flow cytometry, retinal cryosection histology, retinal flatmount immunohistochemistry and vascular imaging, with and without 3K3A-APC treatment. LPS triggered robust inflammatory cell recruitment in the posterior chamber. The 3K3A-APC treatment significantly decreased leukocyte numbers and inhibited leukocyte extravasation from blood vessels into the retinal parenchyma to a level similar to controls. Resident microglia, which underwent an inflammatory transition following LPS injection, remained quiescent in eyes treated with 3K3A-APC. An inflammation-associated increase in retinal thickness, observed in LPS-injected eyes, was diminished by 3K3A-APC treatment, suggesting its clinical relevancy. Finally, 3K3A-APC treatment inhibited inflammasome activation, determined by lower levels of NLRP3 and its downstream effector IL-1β. Our results highlight the anti-inflammatory properties of 3K3A-APC in ocular inflammation and suggest its potential use as a novel treatment for retinal diseases associated with inflammation.

Acute lung inflammation induced by zinc oxide nanoparticles: Evolution and intervention via NRF2 activator

Zinc oxide nanoparticles (ZnONPs) are widely used worldwide. Human inhalation exposure to ZnONPs induces acute lung inflammation (ALI); however, the characteristics and therapeutic targets of ALI are unclear. In this study, female C57BL/6J mice were subjected to a single intratracheal instillation of 20 μg of ZnONPs. Increased lung malondialdehyde levels and decreased total antioxidant capacity at 6 h, as well as increased lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) at 1 day (d) post treatment were observed. A significant inflammatory response was observed at 3 d and 7 d, as evidenced by increased leukocyte numbers and total protein concentration in BALF, and histological abnormalities. Pulmonary NRF2 signaling was significantly activated at 3 d post treatment. To investigate a protective role of NRF2 activator against ZnONP-induced ALI, the mice were intraperitoneally injected with 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) (2 mg/kg) 1 d before and 1 d after ZnONPs treatment. CDDO-Im significantly decreased leukocyte numbers and total protein concentration in BALF and pulmonary inflammatory gene expression, and ameliorated histopathological abnormalities induced by ZnONPs. Collectively, the present study indicates that ZnONPs exposure leads to oxidative stress, cell injury and inflammation in the lung successively. Moreover, the NRF2 activator protects against ZnONPs-induced ALI.

Treatment with the 5-Lipoxygenase Antagonist Zileuton Protects Mice from Postoperative Ileus

Introduction: Previous work of our group showed that lipoxygenase (LOX) pathways become activated upon surgical manipulation of the bowel wall and revealed a beneficial immune modulating role of the LOX-derived anti-inflammatory mediator protectin DX in postoperative ileus (POI). While we found a particular role of 12/15-LOX in the anti-inflammatory LOX action during POI, the role of 5-LOX, which produces the pro-inflammatory leukotriene B4 (LTB4), remained unknown. The purpose of this study was to investigate the role of 5-LOX within the pathogenesis of POI in a mouse model. Methods: POI was induced by intestinal manipulation (IM) of the small bowel in C57BL/6, 5-LOX−/−, and CX3CR1GFP/+. Mice were either treated with a vehicle or with the synthetic 5-LOX antagonist zileuton or were left untreated. Cellular localization of 5-LOX and LTB4 release were visualized by immunofluorescence or ELISA, respectively. POI severity was quantified by gastrointestinal transit (GIT) and leukocyte extravasation into the muscularis externa (ME) by immunohistochemistry. Results: 5-LOX expression was detected 24 h after IM within infiltrating leukocytes in the ME. LTB4 levels increased during POI in wild type but not in 5-LOX−/− after IM. POI was ameliorated in 5-LOX−/− as shown by decreased leukocyte numbers and normalized GIT. Zileuton normalized the postoperative GIT and reduced the numbers of infiltrating leukocytes into the ME. Discussion/Conclusion: Our data demonstrate that 5-LOX and its metabolite LTB4 play a crucial role in POI. Genetic deficiency of 5-LOX and pharmacological antagonism by zileuton protected mice from POI. 5-LOX antagonism might be a promising target for prevention of POI in surgical patients.

TREATMENT OF ACUTE INTESTINAL INFECTION IN MINKS

The article presents the results of studies on the effectiveness of the multicomponent drug Nifulin (powder for oral administration) in the treatment of acute gastrointestinal infection in minks. The active pharmaceutical ingredients (API) of the drug are metronidazole, furazolidone and oxytetracycline hydrochloride. The researches were conducted on 135 minks of standard dark brown breed at the age of 4–5 months with acute gastrointestinal infection. To isolate and identify pathogens from sick minks with intestinal infection, samples of feces were taken, and from animal’s corpses – samples of parenchymal organs. On the basis of clinical signs of the disease and results of bacteriological researches of biomaterial, a diagnosis – salmonellosis has been put. The test for the sensitivity of bacteria-isolates to oxytetracycline showed a high degree of sensitivity of isolated strains of Salmonella to this antibiotic.
 Nifulin was administered orally at a dose of 0,3g/kg body weight with food three times a day for 3 days. For laboratory tests blood sampling was performed from 10 animals before treatment and on the 10th day from the latest application of the drug.
 Morphological studies of blood samples of sick minks before treatment established a significant increase in the number of leukocytes, and in leukoformula – an increased relative number of rod-nucleated neutrophils and lymphocytes, a decreased number of segmentonuclear neutrophils. Biochemical studies of blood serum revealed a decrease in total protein content, increased transaminase enzyme activity and increased urea and creatinine content, compared with physiological norms.
 On the 10th day after antibiotic therapy hematological studies established a reliable decrease in the relative number of leukocytes by 65,4%, in the number of rod-nucleated neutrophils by 1,3 times and in the number of lymphocytes by 1,9 times, an increase in the number of segmentonuclear neutrophils by 1,4 times. The results of biochemical tests of mink’s serum blood indicated a reliable increase in the total protein content by 18% and increased ALT and AST enzyme activity, compared with the physiological values. The increase in serum AST activity in 1.8 times was noted, that can be explained, as a consequence of the disease, and the influence of antibiotics on the mink’s liver functional state. In this case, a decrease in urea content in 1.3 times and creatinine content – in 1.5 times was determined, the values of these indicators were normalized, indicating the restoration of the physiological state of the mink’s kidneys.
 As a result of the treatment of minks the clinical signs of the disease were gradually disappeared: diarrhea stopped, body temperature and respiratory frequency normalized, general condition has improved. In most animals (130 goals) clinical recovery came. During the application of Nifulin manifestations of adverse reactions or negative effects in the experimental minks were not observed.

Sex differences of subpopulation composition of lymphocytes in the peripheral blood in experimental acute and chronic ulcerative colitis

We studied sex differences lymphocytes subpopulations of peripheral blood in adult C57Bl/6 mice during acute and chronic colitis, induced with 1% DSS. We measured subpopulations of lymphocytes with flow cytometry. We showed that in the control group the female mice had statistically significantly higher values of the relative number of regulatory and cytotoxic T lymphocytes comparing to the males. During acute colitis the females showed an increase in the relative number of Thelpers and a decrease of cytotoxic Tlymphocytes, which reflects the activation of immune response. The males had a decrease in the absolute number of leukocytes, lymphocytes and cytotoxic and regulatory T lymphocytes, probably because of an increase in migration of these cells to the inflammation locus and local lymph nodes. In chronic colitis the females had a decrease in the absolute number of leukocytes, lymphocytes, T helpers, cytotoxic T lymphocytes and B lymphocytes when comparing with acute colitis. During chronic colitis the males had a decrease in the absolute number of T helpers and B lymphocytes but an increase of regulatory T cells in comparison with the control group; in comparison with acute colitis the males with chronic colitis had higher relative and absolute number of regulatory T cells. The increase of T regulatory lymphocytes is due to an increase in their proliferation rate in the thymus and increase of their migration to the inflammatory locus – the colon. Future clinical studies may be based on these results, which show that the treatment of colitis, especially with immunotropic agents, must take sex differences into account.

ACCOMPANYING PHYTOTHERAPY - AS PREVENTION OF IMMUNOLOGICAL COMPLICATIONS OF SPECIAL TREATMENT IN PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

In a randomized clinical study, the effect of accompanying therapy with drugs from medicinal plants (phytotherapy) on the dynamics of blood immunological parameters in patients with locally advanced cervical cancer during special treatment was studied. In both groups: the main, receiving phytotherapy, and the comparison group, a decrease in the total number of leukocytes, lymphocytes in peripheral blood, a decrease in the number of CD4+ and CD8+ lymphocytes and the ratio of CD4+/CD8+ during treatment was found. All patients had multidirectional dynamics of levels of immunoglobulins of classes A, G and M in blood. In the main group, immunological status indicators were higher than in the comparison group, and these differences were statistically significant.

The transcriptomic response to irinotecan in colon carcinoma bearing mice preconditioned by fasting.

BackgroundIrinotecan use is limited due to severe toxicity. Preconditioning by fasting (PBF) protects against side effects of irinotecan while preserving its antitumor activity. The mechanisms underlying the effects of PBF still need to be elucidated. Here, we investigated the transcriptional responses of PBF on irinotecan in both tumor and healthy liver tissue.Experimental approachMale BALB/c mice were subcutaneously injected with C26 colon carcinoma cells. Twelve days after tumor inoculation, two groups were fasted for three days and two groups were allowed food ad libitum (AL). Subsequently, both groups received one dose of irinotecan. Twelve hours after administration mice were sacrificed and blood, tumor and liver tissue were harvested. Blood samples were analyzed to determine liver, kidney and bone marrow function, tissues were used for transcriptome analyses.Key resultsThe AL irinotecan group showed worsened organ function and decreased leukocyte numbers. These effects were abated in PBF animals. PBF led to an altered transcriptional response in the liver of irinotecan-treated mice, including decreased cellular injury and increased stress resistance. Hepatic metabolism of irinotecan was also significantly changed due to PBF. The transcriptional response of tumor tissue observed after PBF was hardly affected compared to AL fed animals.ConclusionsTranscriptional changes after PBF to irinotecan treatment showed an improved protective stress response in healthy liver but not in tumor tissue, including changes in irinotecan metabolism. These data help to unravel the mechanisms underlying the effects of fasting on irinotecan and help to improve outcome of chemotherapeutic treatment in cancer patients.

Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model

Background: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. Methods: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. Results: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam₃CSK₄. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. Conclusions: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2.

ЭФФЕКТИВНОСТЬ ПРИМЕНЕНИЯ ОРГАНИЧЕСКОЙ ФОРМЫ ЙОДА В ПИТАНИИ ХРЯКОВ-ПРОИЗВОДИТЕЛЕЙ

The purpose of research is improvement of clinical and physiological state of the organism breeding boars and prevention of iodine deficiency by introducing a basic diet of organic form bioiodine – feed additive «Prost». Production experience on breeding boars Landrace breed – research was conducted. By the principle of analogues, two boars group was formed. The animals were kept under identical conditions. All boars producers received the same feed SC-2 with the same content of metabolizable energy. Diet contain in its composition: 45% barley, 30% wheat; 5% corn; 20% of bvmd. Boars-producers of the control group fed a basic diet (RR) without additives, which conforms to the standards VIZH for this age group. The animal feed of the experimental group were injected with 200 mg per head per day of the feed additive «Prost». Blood for morfogematological studies were taken from the jugular vein at the same time, the chime before feeding. The scientific-production experiment studied the effect of the feed additive «simple» biochemical and morphological parameters of blood boars. As a result of studies, it was found that the inclusion in the diet of the treated group fodder additive, organic iodine content of globulins in the serum of experimental animals was by 5.1% higher than the control group, total protein 7.6%, respectively. The number of red blood cells in the animals in the group with the addition of a «simple» for the test period was higher by 22.1%, 22.1% of red blood cells, hematocrit 17.1%, compared to the control. The study of the white blood boars – when fed feed manufacturers «just» supplements in the experimental animals was observed decrease in the total number of leukocytes by 5.8%, which contributed to the increase of protective and adaptive reactions and reduced antigenic, toxicological stress for the body, the iodine content to an increase in whole blood by 43.8 and 246.3% for the bristles, thyroxine T4 6.5% compared with the control group.

Experimental study of antitumour activity and effects on leukocyte count of intraperitoneal administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet in a rat model of ovarian cancer

Survival of rats with advanced ovarian cancer after intraperitoneal (i.p.) administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet and effects of these treatment modalities on leukocyte count were evaluated in two independent series of experiments. Hyperthermic intraperitoneal chemoperfusion with dioxadet (15 mg/kg) provided median survival of rats of 49 days (95% CI 28–70), i.p. administration of dioxadet (1.5 mg/kg) of 28 days (95% CI 16–36; P = 0.020). Single i.p. injection of dioxadet caused a significant decrease in total number of leukocytes (17–52%), granulocytes (18–75%), lymphocytes (18–62%) and monocytes (12–46%) in the peripheral blood of tumour-bearing rats compared to untreated animals. After HIPEC with dioxadet, the total number of leukocytes, granulocytes, lymphocytes and monocytes in peripheral blood of rats remained significantly higher than the corresponding values in the group with dioxadet.

Effects of positive blood alcohol concentration on outcome and systemic interleukin-6 in major trauma patients

BackgroundThe influence of alcohol on the outcome after major trauma remains controversial. In several recent studies, alcohol has been associated with neuroprotective effects in head injuries, while others reported negative or no effects on survival and/or the in-hospital stay in major trauma patients (TP). The purpose of this study was to examine the relationship of alcohol with injury characteristics and outcome as well as to analyze possible anti-inflammatory properties in major TP. Patients/methods184 severely injured TP with an Injury Severity Score (ISS) ≥16 were successively enrolled. All patients had measured blood alcohol concentration (BAC). Patients were grouped according to their positive BAC (>0.5‰, BAC) vs. <0.5‰ alcohol (no BAC) upon arrival at the emergency department (ED). Injury characteristics, physiologic parameters and outcome with respect to organ or multiple organ failure (MOF), SIRS, sepsis, pneumonia, ARDS or mortality were assessed. Systemic levels of interleukin (IL)-6 at ED were determined. ResultsForty-nine TP had positive BAC without chronic alcohol abuse history and 135 patients had BAC levels below 0.5‰. Overall injury severity and age were comparable in both groups. No BAC TP received significantly higher numbers of packed red blood cells and fresh frozen plasma (transfused within the initial 24h or in total) compared to BAC TP. Organ failure, MOF, SIRS, sepsis, pneumonia, ARDS and the in-hospital mortality were not different between both groups. Trauma patients with positive BAC had significantly decreased leukocyte numbers and systemic IL-6 levels compared to no BAC group. There was a significant positive correlation between leukocyte counts and IL-6 as well as BAC and leukocytes. BAC levels did not correlate with IL-6. ConclusionsPositive BAC is associated with reduced leukocyte numbers and lowered systemic IL-6 levels at admittance indicating immune-suppressive effects of alcohol in major trauma patients.

Targeting Interleukin-1β Reduces Leukocyte Production After Acute Myocardial Infarction.

Myocardial infarction (MI) is an ischemic wound that recruits millions of leukocytes. MI-associated blood leukocytosis correlates inversely with patient survival, yet the signals driving heightened leukocyte production after MI remain incompletely understood. With the use of parabiosis surgery, this study shows that soluble danger signals, among them interleukin-1β, increase bone marrow hematopoietic stem cell proliferation after MI. Data obtained in bone marrow reconstitution experiments reveal that interleukin-1β enhances hematopoietic stem cell proliferation by both direct actions on hematopoietic cells and through modulation of the bone marrow's hematopoietic microenvironment. An antibody that neutralizes interleukin-1β suppresses these effects. Anti-interleukin-1β treatment dampens the post-MI increase in hematopoietic stem cell proliferation. Consequently, decreased leukocyte numbers in the blood and infarct reduce inflammation and diminish post-MI heart failure in ApoE(-/-) mice with atherosclerosis. The presented insight into post-MI bone marrow activation identifies a mechanistic target for muting inflammation in the ischemically damaged heart.

In vivo confocal microscopy for the detection of canine fungal keratitis and monitoring of therapeutic response.

To describe invivo corneal confocal microscopy of dogs during the clinical course of fungal keratitis and correlate findings with clinical evaluations and an exvivo experimental canine fungal keratitis model. Seven dogs with naturally acquired fungal keratitis and exvivo canine corneas experimentally infected with clinical fungal isolates. Dogs with naturally acquired fungal keratitis were examined by invivo laser scanning confocal microscopy. Initial confocal microscopic examinations were performed to assist in establishing the diagnosis of fungal keratitis. Serial confocal microscopic examinations were performed to guide antifungal chemotherapy. Confocal microscopy images of canine corneal fungal isolates were obtained by examination of experimentally infected exvivo canine corneas to corroborate invivo findings. Fungi cultured and detected by PCR from canine corneal samples included Candida albicans, Fusarium incarnatum-equiseti, Malassezia pachydermatis, and a Rhodotorula sp. Linear, branching, interlocking, hyperreflective structures were detected by confocal microscopy in dogs with filamentous fungal keratitis and round to oval hyperreflective structures were detected in dogs with yeast fungal keratitis. Antifungal chemotherapy was associated with a progressive reduction in the distribution and density of corneal fungal elements, alterations to fungal morphology, decreased leukocyte numbers, restoration of epithelial layers, and an increased number of visible keratocyte nuclei. No dogs had a recurrence of fungal keratitis following medication discontinuation. Confocal microscopic fungal morphologies were similar between invivo and exvivo examinations. In vivo corneal confocal microscopy is a rapid method of diagnosing fungal keratitis in dogs and provides a noninvasive mechanism for monitoring therapeutic response.

Metabolic profile and ruminal and abomasal pH in sheep subjected to intravenous ranitidine

Resumo: Brazilian sheep production has intensified, predisposing sheep to an increased incidence of digestive disorders, such as abomasal ulcers. Ranitidine is used to prevent and treat this disease; however, there is little information on the parenteral use of this drug in adult ruminants. Few data exist on the concomitant metabolic changes and the behavior of the digestive system associated with its use. For this study, five healthy male sheep with ruminal and abomasal cannulas were used. A 5x5 Latin square experiment with a 2x2+1 factorial arrangement of the treatments was performed. Sheep treated with drug doses of 1 or 2mg/kg ranitidine administered intravenously every 8 or 12 hours were compared with the control group, was treated intravenously with 1 mL of physiological solution per 25 kg every 12 hours. Higher total protein concentrations, hemoglobin levels, as well as increased aspartate aminotransferase activity and increased abomasal pH for up to 150 min following drug administration were observed in all animals that received the drug, regardless of dose and frequency. The animals treated every 12 hours showed a decrease in leukocyte number compared with the control group and with the animals treated every 8 hours. Increased serum creatinine concentrations were observed in the animals treated every 8 hours. Treatments of 1mg/kg every 8 hours and 2mg/kg every 12 hours increased the red blood cell count and decreased the serum pepsinogen. All protocols studied were safe for healthy sheep, but 1mg/kg ranitidine every 8 hours and 2mg/kg ranitidine every 12 hours were the most effective protocols for gastric protection.

Pistacia chinensis: a potent ameliorator of CCl₄ induced lung and thyroid toxicity in rat model.

In the current study protective effect of ethanol extract of Pistacia chinensis bark (PCEB) was investigated in rats against CCl4 induced lung and thyroid injuries. PCEB dose dependently inhibited the rise of thiobarbituric acid-reactive substances, hydrogen peroxide, nitrite, and protein content and restored the levels of antioxidant enzymes, that is, catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, γ-glutamyl transpeptidase, and quinone reductase in both lung and thyroid tissues of CCl4 treated rats. Decrease in number of leukocytes, neutrophils, and hemoglobin and T3 and T4 content as well as increase in monocytes, eosinophils, and lymphocytes count with CCl4 were restored to normal level with PCEB treatment. Histological study of CCl4 treated rats showed various lung injuries like rupture of alveolar walls and bronchioles, aggregation of fibroblasts, and disorganized Clara cells. Similarly, histology of CCl4 treated thyroid tissues displayed damaged thyroid follicles, hypertrophy, and colloidal depletion. However, PCEB exhibited protective behaviour for lungs and thyroid, with improved histological structure in a dose dependant manner. Presence of three known phenolic compounds, that is, rutin, tannin, and gallic acid, and three unknown compounds was verified in thin layer chromatographic assessment of PCEB. In conclusion, P. chinensis exhibited antioxidant activity by the presence of free radical quenching constituents.

Salivary Glands of Female Ticks Rhipicephalus sanguineus Like a Potential Source of Molecules with Inhibitory Action: In vivo study with Walker 256 Tumor Cells

This study evaluated the effects of one or two injection of differents concentrations (0.2 and 0.04μg/μL) of extracts obtained from the salivary glands of female ticks Rhipicephalus sanguineus (Acari: Ixodidae) (Latreille, 1806) also called “brown dog tick” fed for 2 days on the rabbit hosts on the morpho-physiology of the leg musculature of female Wistar rats inoculated with Walker 256 tumor cells. The number of leukocytes and the creatinine levels were quantified for individuals from all groups. The results of both histology and electron microscopy revealed that a single, low-concentration injection of the extract (0.04μg/μL) was more effective in containing tumor invasion and caused less ‘collateral damage’ to the muscle tissue, which was the object of this study. The results also revealed that creatinine levels were higher in rats subjected to both one and two injections of the extract at a concentration of 0.04μg/μL than in those subjected to one and two injections of the extract at the higher concentration (0.2μg/μL), suggesting that in the first group, injection of the extract contributed to maintaining the integrity of the muscle tissue. With regard to the number of leukocytes, the results suggested that in all the inoculated rats (Walker 256 cells), there was a significant increase in the total number of leukocytes. The inoculated rats that received both one and two injections of the extract at a concentration of 0.2μg/μL experienced a significant increase in the number of leukocytes compared with those inoculated but not exposed to the extract; this result can be explained by the fact that beyond the tumor cells, the extract itself acted to boost the defense response at this concentration. However, inoculated rats subjected to injections (one and two) of the extract at a concentration of 0.04μg/μL showed a significant decrease in the total number of leukocytes compared with rats that were only inoculated and those inoculated and injected with the extract at a concentration of 0.2μg/μL. These results reinforced that the extract at the 0.04μg/μL concentration not only acted more effectively to inhibit Walker 256 tumor cells but also did not act as a stressor, because the number of leukocytes was lower. Therefore, the data obtained here indicated that the same molecules or a pool of molecules produced by the salivary glands of ticks belonging to this species have the ability to inhibit tumor growth, while minimizing ‘collateral damage’ to the body.

Leukocyte Activity Is Altered in a Ground Based Murine Model of Microgravity and Proton Radiation Exposure

Immune system adaptation during spaceflight is a concern in space medicine. Decreased circulating leukocytes observed during and after space flight infer suppressed immune responses and susceptibility to infection. The microgravity aspect of the space environment has been simulated on Earth to study adverse biological effects in astronauts. In this report, the hindlimb unloading (HU) model was employed to investigate the combined effects of solar particle event-like proton radiation and simulated microgravity on immune cell parameters including lymphocyte subtype populations and activity. Lymphocytes are a type of white blood cell critical for adaptive immune responses and T lymphocytes are regulators of cell-mediated immunity, controlling the entire immune response. Mice were suspended prior to and after proton radiation exposure (2 Gy dose) and total leukocyte numbers and splenic lymphocyte functionality were evaluated on days 4 or 21 after combined HU and radiation exposure. Total white blood cell (WBC), lymphocyte, neutrophil, and monocyte counts are reduced by approximately 65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered at both time points investigated. At 21 days post-exposure to combined HU and proton radiation, T cell activation and proliferation were assessed in isolated lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is decreased by 30% in the combined treatment group, compared to the non-treated control group and cell proliferation was suppressed by approximately 50%, compared to the non-treated control group. These findings reveal that the combined stressors (HU and proton radiation exposure) result in decreased leukocyte numbers and function, which could contribute to immune system dysfunction in crew members. This investigation is one of the first to report on combined proton radiation and simulated microgravity effects on hematopoietic, specifically immune cells.

Effect of polychemotherapy on leukocytes under acute lymphoblast leukosis in children

Event Abstract Back to Event Effect of polychemotherapy on leukocytes under acute lymphoblast leukosis in children Anatoliy P. Godovalov1*, Olga V. Lebedinskaya2, Nina B. Merzlova2, Irina A. Baranova1 and Artem V. Proskuryakov1 1 Acad. E.A. Wagner Perm State Medical Academy, immunology, Russia 2 Acad. E.A. Wagner Perm State Medical Academy, histology, embriology and cytology, Russia The aim of investigation was the search for toxicity criteria of cytotoxic preparations while using the analysis of blood values’ dynamics following the chemotherapy with cytostatics’ inclusion. The analysis of hematological parameters was carried out in 24 patients at different terms of treatment during the chemotherapy according to AII-MB-2005 protocol. On completion the first course of treatment the sharp decrease in leukocyte number as observed in a day that corresponds to 2-grade hematotoxicity according to WHO’s classification. Thereafter, the parameter elevation was detected that retained to the end of first therapy cycle. During the treatment it was found that the increment in neutrophil content was realized at the expense of the increase in the number of their mature forms. The initial level of peripheral blood blast cells comprised 25% prior to therapy, 7% (3rd day), and 1% (8th day), then all of patients demonstrated 0% that maintained further. Meanwhile the efficient bone marrow hemopoiesis suppression occurred as well. Given that 4% is a standard value and initial background is 89% in average, the amount of bone marrow blast forms was retained at 1,7% level for the 36 days of therapy. All the patients examined after the first course of polychemotherapy (induction of remission) demonstrated the state of hematological remission. Thus, the suppression of bone marrow hemopoiesis under cytostatics’ therapy according to AII-MB-2005 protocol is not excessive and is maintained at the level that allows achieving remission. This work was supported by RFBR grant №11-04-96037r_ural_a and administrative body of Perm Region. Keywords: chemotherapy toxicity, hematological parameters, suppression mechanisms, leukocyte number, bone marrow hemopoiesis Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Godovalov AP, Lebedinskaya OV, Merzlova NB, Baranova IA and Proskuryakov AV (2013). Effect of polychemotherapy on leukocytes under acute lymphoblast leukosis in children. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00547 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Anatoliy P Godovalov, Acad. E.A. Wagner Perm State Medical Academy, immunology, Perm, Russia, AGodovalov@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anatoliy P Godovalov Olga V Lebedinskaya Nina B Merzlova Irina A Baranova Artem V Proskuryakov Google Anatoliy P Godovalov Olga V Lebedinskaya Nina B Merzlova Irina A Baranova Artem V Proskuryakov Google Scholar Anatoliy P Godovalov Olga V Lebedinskaya Nina B Merzlova Irina A Baranova Artem V Proskuryakov PubMed Anatoliy P Godovalov Olga V Lebedinskaya Nina B Merzlova Irina A Baranova Artem V Proskuryakov Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.