Selective Biological Effects of Selenium-Enriched Polysaccharide (Se-Le-30) Isolated from Lentinula edodes Mycelium on Human Immune Cells.

A common edible mushroom Lentinula edodes, is an important source of numerous biologically active substances, including polysaccharides, with immunomodulatory and antitumor properties. In the present work, the biological activity of the crude, homogenous (Se)-enriched fraction (named Se-Le-30), which has been isolated from L. edodes mycelium by a modified Chihara method towards human peripheral blood mononuclear cells (PBMCs) and peripheral granulocytes, was investigated. The Se-Le-30 fraction, an analog of lentinan, significantly inhibited the proliferation of human PBMCs stimulated with anti-CD3 antibodies or allostimulated, and down-regulated the production of tumor necrosis factor (TNF)-α by CD3+ T cells. Moreover, it was found that Se-Le-30 significantly reduced the cytotoxic activity of human natural killer (NK) cells. The results suggested the selective immunosuppressive activity of this fraction, which is non-typical for mushroom derived polysaccharides.

Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.

Pre-clinical evaluation of an innovative oral nano-formulation of baicalein for modulation of radiation responses.

There is an unmet medical need for non-toxic and effective radiation countermeasures for prevention of radiation toxicity during planned exposures. We have earlier shown that intraperitoneal administration of baicalein (BCL) offers significant survival benefit in animal model. Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of baicalein has been reported in pre-clinical model systems and also in healthy human volunteers. However, clinical translation of baicalein is hindered owing to poor bioavailability due to lipophilicity. In view of this, we fabricated and characterized in-situ solid lipid nanoparticles of baicalein (SLNB) with effective drug entrapment and release kinetics. SLNB offered significant protection to murine splenic lymphocytes against 4 Gy ionizing radiation (IR) induced apoptosis. Oral administration of SLNB exhibited ~70% protection to mice against whole body irradiation (WBI 7.5 Gy) induced mortality. Oral relative bioavailability of BCL was enhanced by over ~300% after entrapment in the SLNB as compared to BCL. Oral dosing of SLNB resulted in transient increase in neutrophil abundance in peripheral blood. Interestingly, we observed that treatment of human lung cancer cells (A549) with radioprotective dose of SLNB exhibited radio-sensitization as evinced by decrease in survival and clonogenic potential. Contrary to antioxidant nature of baicalein in normal cells, SLNB treatment induced significant increase in cellular ROS levels in A549 cells probably due to higher uptake and inhibition of TrxR. Thus, a pharmaceutically acceptable SLNB exhibited improved bioavailability, better radioprotection to normal cells and sensitized cancer cells to radiation induced killing as compared to BCL suggesting its possible utility as an adjuvant during cancer radiotherapy.

Inhibitory Effects of Green Asparagus Extract, Especially Phospholipids, on Allergic Responses in Vitro and in Vivo.

Asparagus (Asparagus officinalis L.) is one of the widely consumed vegetables. To investigate the mechanism underlying the anti-allergic responses of asparagus, we extracted different fractions from asparagus and measured their inhibitory effects on ß-hexosaminidase release in RBL-2H3 cells in vitro and an atopic dermatitis NC/Nga mouse model in vivo. The lipid fractions from asparagus were extracted with 50% ethanol, separated using chloroform by liquid-liquid phase separation, and fractionated by solid-phase extraction. Among them, acetone fraction (rich in glycolipid) and MeOH fraction (rich in phospholipid) markedly inhibited ß-hexosaminidase release from RBL-2H3 cells. In NC/Nga mice treated with picryl chloride, atopic dermatitis was alleviated following exposure to the 50% EtOH extract, acetone fraction, and methanol fraction. The inhibitory effects of asparagus fractions in vivo were supported by the significant decrease in serum immunoglobulin E (IgE) levels. The phospholipid fractions showed significantly better inhibitory effects, and phosphatidic acid from this fraction showed the best inhibitory effect on ß-hexosaminidase release. In mice challenged with ovalbumin (OVA), oral administration of asparagus extract and its fractions decreased the OVA-specific IgE level and total IgE, indicating that these effects may be partly mediated through the downregulation of antigen-specific IgE production. Taken together, the present study shows for the first time that asparagus extract and its lipid fractions could potentially mitigate allergic reactions by decreasing degranulation in granulocytes. Our study provides useful information to develop nutraceuticals and functional foods fortified with asparagus.

Selenium-containing polysaccharides from Lentinula edodes-Biological activity.

We hypothesized that selenium(Se)-enriched polysaccharides would possess superior biological activity when compared to those non-enriched. To verify this hypothesis, we obtained by biotechnological methods a Se-enriched analog of Japanese anticancer drug lentinan and, as a reference, the non-Se-enriched fraction. We tested the effects of the obtained fractions on the proliferation of human peripheral blood mononuclear cells. The results suggested a selective immunosuppressive activity, non-typical for mushroom derived polysaccharides. Both fractions caused significant inhibition of human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. The inhibitory effect was not due to the toxicity of the examined polysaccharides. In normal (HUVEC) or malignant (HeLa) cells tested fractions significantly enhanced cell viability and protected the cells from oxidative stress conditions. However, we observed no effect of the polysaccharide fractions on the production of reactive oxygen species by granulocytes in vitro. The selenium content increased the biological activity of the tested polysaccharide fractions.

Antimicrobial and Immunomodulatory Effect of Gum Arabic on Human and Bovine Granulocytes Against Staphylococcus aureus and Escherichia coli.

Gum arabic (GA) is a traditional herbal medicine from Acacia Senegal (L.) Willdenow trees, which consist of a complex mixture of polysaccharides and glycoproteins. It is used in daily applications for several diseases and is considered to protect against bacterial infections. The detailed mechanisms behind these observations are still unclear. In this study, we investigated the direct antibacterial activity of GA water and ethanol extracts against Staphylococcus (S.) aureus or Escherichia (E.) coli and the immunomodulating properties of those extracts on granulocytes as a first line of defense against bacteria. Firstly, the direct antimicrobial effect of GA was tested on three different S. aureus strains and two E. coli strains. The growth of bacteria was analyzed in the presence of different GA concentrations over time. GA water as well as ethanol extracts showed a significant growth inhibition in a concentration-dependent manner in the case of S. aureus Newman, S. aureus Rd5, and E. coli 25922, but not in the case of S. aureus USA300 and E. coli K1. Transmission electron microscopic analysis confirmed an antibacterial effect of GA on the bacteria. Secondly, the immunomodulatory effect of GA on the antimicrobial activity of bovine or human blood-derived granulocytes was evaluated. Interestingly, water and ethanol extracts enhanced antimicrobial activity of granulocytes by the induction of intracellular ROS production. In line with these data, GA increased the phagocytosis rate of E. coli. No effect was seen on neutrophil extracellular trap (NET) formation that mediates killing of extracellular bacteria such as S. aureus. In conclusion, we show that GA exhibits a direct antibacterial effect against some S. aureus and E. coli strains. Furthermore, GA boosts the antimicrobial activities of granulocytes and increases intracellular ROS production, which may lead to more phagocytosis and intracellular killing. These data might explain the described putative antimicrobial activity of GA used in traditional medicine.

Modification of the Myelotoxic and Antitumor Effects of Polychemotherapy by Polysaccharides from Tussilago farfara L.

The experiments on C57Bl/6 mice with Lewis lung carcinoma showed that addition of Tussilago farfara L. polysaccharides to conventional cisplatin/paclitaxel polychemotherapy moderated neutropenia caused by antitumor therapy and increased its efficiency. The stimulating effect of polysaccharides on the granulopoietic lineage cells is comparable with that of recombinant CSF Neupogen.

Comparative toxicity of Corexit® 9500, oil, and a Corexit®/oil mixture on the eastern oyster, Crassostrea virginica (Gmelin).

Given their particle feeding behavior, sessile nature, and abundance in coastal zones, bivalves are at significant risk for exposure to oil and oil dispersant following environmental disasters like the Deepwater Horizon oil spill. However, the effects of oil combined with oil dispersants on the health of oysters are not well studied. Therefore, eastern oysters (Crassostrea virginica) were exposed in vivo to Corexit® 9500, crude oil (high-energy water accommodated fraction; HEWAF), and a Corexit®/oil mixture (chemically-enhanced water accommodated fraction; CEWAF) to evaluate potential toxic effects on immunological (phagocytosis and respiratory burst), physiological (feeding rate), and histological endpoints. Phagocytosis was significantly increased following CEWAF exposure only. Respiratory burst was significantly decreased following Corexit® exposure, but significantly increased following exposure to the highest concentration of CEWAF. Oyster feeding rates were significantly decreased following exposure to Corexit®, HEWAF, and CEWAF, and were most sensitive to CEWAF exposure. These modulations of important immunological and physiological functions could result in serious health outcomes for oysters, such as increased parasitism and decreased growth. Our experiments showed that subtle, sub-lethal effects occurred following acute in vivo exposure to Corexit®, HEWAF, and CEWAF, though oysters were not equally sensitive to the three components. Data from this study can be used for more accurate risk assessment concerning the impact of oil and Corexit® on the health of oysters.

Dietary supplementation with mannan oligosaccharide and clinoptilolite modulates innate and adaptive immune parameters of weaned pigs.

The aim of this study was to assess modulatory effects of dietary supplements mannan oligosaccharide (MOS) and clinoptilolite (CPL) as potential alternatives to antibiotic growth promoters (AGP) given to 4-week old pigs at weaning (Day 0) on their innate/adaptive immunity by determining: alterations in C-reactive protein (CRP) and haptoglobin (HpG) serum levels, efficiency of blood monocytes (MO) and neutrophilic granulocytes (GR) for in vitro phagocytosis (PHC)/microbicidity (MBC) and proportion of extrathymic double positive CD4 CD8 (CD4+CD8+) T cells throughout 35 days of the study. Neither MOS nor CPL changed the serum concentrations of CRP, whereas that of HpG was significantly increased in the CPL supplemented pigs (p<0.05) at Day 35. Activity of PHA of GR was significantly increased by both dietary supplements (p<0.05) from Day 7 to Day 35. Also, the GR from pigs fed with both supplements had significantly increased MBC at Day 7 (p<0.05), but at Day 35 such an increase was observed only for CPL. The in vitro PHC/MBC of MO did not change in either group of supplemented pigs. The pigs supplemented with MOS had a significantly higher proportion of CD4+CD8+ T lymphocytes at Day 28 (p<0.05). Although both supplements showed a promising ability to stimulate rather innate than adaptive cellular immunity, it does not appear that any solely applied natural substance such as MOS or CPL in the current study could be a competitive alternative to conventional AGP for improving health and promoting growth in weaned pigs.

[Analyzing Effect of Shenmai Injection on Levels of WBC and Neutrophilic Granulocytes Using Propensity Score Method].

Objective To observe the effect of Shenmai Injection (SI) on levels of white blood cell (WBC) and neutrophilic granulocyte. Methods Case data in Hospital Information System ( HIS) were collected including patients who used SI (as the experimental group) and those who unused SI (as the control group). Data of their WBC and neutrophilic granulocyte in routine blood test were extracted. The bias of confounding factors were balanced based by propensity score matching (PSM). Data were analyzed using X² test. Results The samples after being matched (0. 661 ) was less than the samples before being matched (0. 710). Totally 5 138 cases were successfully matched in the total of 7 256 cases in the control group. There was statistical difference in increased levels of WBC and neutrophilic granulo- cyte between the two groups (X² =10. 312 ,P = 0. 027; X² =14. 228 ,P =0. 013). There was no statistical difference in decreased levels of WBC and neutrophilic granulocyte between the two groups (X² =1. 385, P = 0. 536; X² = 2. 339,P = 0. 126). Conclusion Results based the data of HIS and present research methods showed that SI might have effect on increased levels of WBC and neutrophilic granulocyte, but no effect on their decreased changes.

GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations.

OBJECTIVE: Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b(+)/Ly6C(hi)) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: (1) prevent stress-induced peripheral and central inflammatory responses, and (2) block anxiety and social avoidance behavior in mice subjected to RSD. METHODS: C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25mg/kg) or vehicle (0.9% NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD. RESULTS: Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b(+)/CD45(high)) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and depressive-like behavior in mice exposed to RSD. CONCLUSION: These data support the notion that lorazepam and clonazepam, aside from exerting anxiolytic and antidepressant effects, may have therapeutic potential as neuroimmunomodulators during psychosocial stress. The reversal of RSD-induced behavioral outcomes may be due to the enhancement of GABAergic neurotransmission, or some other off-target effect. The peripheral actions of lorazepam, but not clonazepam, seem to be mediated by TSPO activation.

Amelioration of Atherosclerosis by the New Medicinal Mushroom Grifola gargal Singer.

The beneficial effects of edible mushrooms for improving chronic intractable diseases have been documented. However, the antiatherogenic activity of the new medicinal mushroom Grifola gargal is unknown. Therefore, we evaluated whether Grifola gargal can prevent or delay the progression of atherosclerosis. Atherosclerosis was induced in ApoE lipoprotein-deficient mice by subcutaneous infusion of angiotensin II. Grifola gargal extract (GGE) was prepared and intraperitoneally injected. The weight of heart and vessels, dilatation/atheroma formation of thoracic and abdominal aorta, the percentage of peripheral granulocytes, and the blood concentration of MCP-1/CCL2 were significantly reduced in mice treated with GGE compared to untreated mice. By contrast, the percentage of regulatory T cells and the plasma concentration of SDF-1/CXCL12 were significantly increased in mice treated with the mushroom extract compared to untreated mice. In vitro, GGE significantly increased the secretion of SDF-1/CXCL12, VEGF, and TGF-ß1 from fibroblasts compared to control. This study demonstrated for the first time that Grifola gargal therapy can enhance regulatory T cells and ameliorate atherosclerosis in mice.

Nardostachys chinensis induces granulocytic differentiation with the suppression of cell growth through p27(Kip1) protein-related G0/G1 phase arrest in human promyelocytic leukemic cells.

CONTEXT: Nardostachys chinensis Batalin (Valerianaceae) has been used in Korean traditional medicine to elicit stomachic and sedative effects. However, the anti-leukemic activities of N. chinensis have not been well examined. OBJECTIVE: To investigate the effect of N. chinensis on differentiation and proliferation in the human promyelocytic leukemic HL-60 cells. MATERIALS AND METHODS: The dried roots and stems of N. chiensis are extracted using hot water and then freeze-dried. The yield of extract was 12.82% (w/w). The HL-60 cells were treated with 25-200 µg/ml of N. chinensis for 72 h or 100 µg/ml of N. chinensis for 24-72 h. RESULTS: Nardostachys chinensis significantly inhibited cell viability dose dependently with an IC50 of 100 µg/ml in HL-60 cells. Nardostachys chinensis induced differentiation of the cells as measured by reduction activity of NBT and expression of CD11b but not of CD14 as analyzed by flow cytometry, which indicates a differentiation toward the granulocytic lineage. Nardostachys chinensis also induced growth inhibition through G0/G1 phase arrest in the cell cycle of HL-60 cells. Among the G0/G1 phase in the cell cycle-related protein, the expression of cyclin-dependent kinase (CDK) inhibitor p27(Kip1) was increased in N. chinensis-treated HL-60 cells, whereas the expression levels of CDK2, CDK4, CDK6, cyclin D1, cyclin D3, cyclin E, and cyclin A were decreased. Interestingly, N. chinensis markedly enhanced the binding of p27(Kip1) with CDK2 and CDK6. DISCUSSION AND CONCLUSION: This study demonstrated that N. chinensis is capable of inducing cellular differentiation and growth inhibition through p27(Kip1) protein-related G0/G1 phase arrest in HL-60 cells.

Arginine and vitamin E improve the immune response after a Salmonella challenge in broiler chicks.

Two experiments were conducted to evaluate the effects of Arg, vitamin E (VE), and mannanoligosaccharide (MOS) on the immune response and clearance of Salmonella in broiler chickens. In each experiment, 1-d-old chicks (n = 160) were randomly distributed into 4 groups: antibiotic-free diet (negative control, CTL-), antibiotic-supplemented diet (positive control, CTL+), antibiotic free-diet plus Arg and VE (AVE), or antibiotic-free diet plus Arg, VE, and MOS (AVM). Birds were orally challenged with 10(6) cfu of a novobiocyn and nalidixic acid-resistant Salmonella enterica serovar Typhimurium strain at d 7 (experiment 1) or at d 3 (experiment 2). Heterophil- (HOB) and monocyte- (MOB) oxidative burst and lymphocyte proliferation (LPR), antibody titers, and Salmonella content in the ceca were measured at several intervals postinfection (PI). In experiment 1, both AVM and AVE decreased HOB compared with the controls 5 and 9 d PI, but increased LPR 9 d PI. In the same experiment, birds fed the AVE diet had higher MOB than birds fed CTL+ or the AVM diet at 7 d PI, whereas 9 d PI birds fed the AVM diet had the highest MOB. In experiment 2, birds fed the AVE diet had higher MOB, HOB, and LPR than birds in the other treatments 7 and 14 d PI, except at 7 d PI, when MOB was not different among treatments. Birds fed the AVM diet had the highest IgA antibody titer, and a higher IgM antibody titer than the CTL+ birds. In experiment 1, Salmonella Typhimurium content in the ceca was lower in birds fed the AVM diet compared with birds fed the CTL- diet 3 d PI, but later on (10 and 17 d PI), and in experiment 2 (7, 14, and 21 d PI), Salmonella Typhimurium concentrations were not different among treatments. Thus, Arg and VE improved immune response after a Salmonella Typhimurium challenge in young chicks, and although they did not reduce Salmonella Typhimurium concentrations in the ceca, they may improve bacterial resistance against other pathogens in commercial growing conditions.

Alcohol- and water-based extracts obtained from Rhodiola rosea affect differently the number and metabolic activity of circulating granulocytes in Balb/c mice.

INTRODUCTION AND OBJECTIVE: Rhodiola rosea (RR) rhizomes with roots extracts are traditional natural drugs originated from Asia and now commonly used as adaptogens and antidepressants. The aim of this work was to study the in vivo effect of aqueous (RRW) and 50% hydro-alcoholic (RRA) extracts on the number and metabolic activity of blood granulocytes in mice. MATERIAL AND METHODS: Mice were fed for 7 days RR extract in daily doses 0.05, 0.1, 0.2 or 0.4 mg. The metabolic activity of blood granulocytes was determined by measuring of their luminol-dependent chemiluminescent activity in scintillation counter, after zymosan stimulation. RESULTS: Number of blood granulocytes was diminished and their chemiluminescence was enhanced in all groups of mice fed R.rosea hydro-alcoholic extract. Aqueous extract (RRW) was ineffective in all doses applied. CONCLUSION: This study revealed difference in the number and metabolic activity of granulocytes mice fed RRA or RRW extracts. Immune characteristics of some individual compounds from RRA and RRW extracts, selected by HPLC analysis, should be carried out in the next experiments.

Nardostachys chinensis induces the differentiation of human promyelocytic leukemic cells through the activation of the protein kinase C-dependent extracellular signal-regulated kinase signaling pathway.

The underground parts of Nardostachys chinensis (N. chinensis), which belongs the genus Valerianaceae, have been used as sedative and analgesic agents in traditional Korean medicine for centuries. The mitogen-activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular responses, such as cell proliferation, differentiation and apoptosis. Protein kinase C (PKC) plays a key role in the regulation of proliferation and differentiation. In this study, we investigated the signaling pathways involved in the differentiation of the HL-60 human leukemic cells induced by N. chinensis extract. Treatment with N. chinensis extract resulted in the activation of the extracellular signal-regulated kinase (ERK) pathway and induced the differentiation of HL-60 cells into granulocytes. The activation of p38 MAPK was also observed 24 h after treatment; however, the activation of c-Jun N-terminal kinase (JNK) was unaffected. Treatment with an inhibitor of ERK (PD98059) blocked the nitrotetrazolium blue chloride (NBT) reducing activity and CD11b expression in the N. chinensis-treated HL-60 cells, whereas treatment with an inhibitor of p38 MAPK (SB203580) had no significant effect on NBT reducing activity and CD11b expression. In addition, N. chinensis extract increased PKC activity and the protein levels of PKCα, PKCßI and PKCßII isoforms, without a significant change in the protein levels of the PKCγ isoform. PKC inhibitors (GF 109203X, chelerythrine and H-7) inhibited the differentiation of HL-60 cells into granulocytes, as well as ERK activation in the N. chinensis-treated HL-60 cells. These results indicate that the PKC and ERK signaling pathways may be involved in the induction, by N. chinensis extract, of the differentiation of HL-60 cells into granulocytes.

Comparison of specific activity of granulocytopoiesis stimulators after treatment with cytostatics with different mechanisms of action.

We compared hemostimulating effects of glyciram, pantohematogen, granulocytic CSF, and D-glucuronic acid preparation on the granulocytic lineage hemopoiesis suppressed by cyclophosphamide or 5-fluorouracil. The effects hemostimulators against the background of 5-fluorouracil treatment were less pronounced that during cyclophosphamide treatment.

The influence of selenium compounds of different structure on morphology, blood biochemistry and phagocytic capability of granulocytes in rats.

BACKGROUND: Selenium belongs to important microelements. Numerous studies have revealed relationships between its deficiency and occurrence of diverse illnesses, but the question of the proper form and dose of Se-supplementation still remains unsolved. OBJECTIVE: In the present study the influence of different selenium compounds on blood morphology and biochemistry as well as on phagocytic capacity of granulocytes and NBT test in rats was investigated. MATERIAL AND METHODS: Adolescent male Wistar rats were divided into four groups (ten animals each): I--control, received saline; II--received sodium selenite Na2SeO3; III--received selenoorganic compound A of chain structure 4-(o-tolyl-)-selenosemicarbazide of 2-chlorobenzoic acid; IV--received selenoorganic compound B of cyclic structure 3-(2-chlorobenzoylamino-)-2-(o-tolylimino-)-4-methyl-4-selenazoline. The administration was performed by stomach tube at a dose of 5 x 10(-4) mg Se g(-1) b.w. once a day for 10 days. RESULTS: Selenium compounds treatment decreased haematocrit. Erythrocytes number was unchanged in all groups receiving Se vs. control, whereas leucocytes number was depressed in groups II and IV. Haemoglobin was significantly decreased in group III. White blood count was altered in groups II and III, where all parameters were markedly decreased except for lymphocytes in group III and remained unchanged in group IV. The outcomes regarding selenium effect on biochemistry parameters of blood showed that urea remained unchanged, glucose was statistically decreased in groups II and III, whereas cholesterol was significantly diminished in group II and increased in group III vs. control. Results concerning phagocytosis and NBT test displayed that % of positive cells were decreased in groups II and III, whereas remained unaltered in group IV vs. control. CONCLUSIONS: As cyclic selenoorganic compound B did not cause many significant changes of the studied parameters it may be suggested that after further researches it could be taken into account as a possible selenium supplement.

Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: an ovalbumin-induced model of allergic airway disease.

Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a 'low dose' model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.

The effect of anti-inflammatory and antimicrobial herbal remedy PADMA 28 on immunological angiogenesis and granulocytes activity in mice.

UNLABELLED: PADMA 28 is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses anti-inflammatory, antioxidant, antimicrobial, angioprotecting, and wound healing properties. The aim of the present study was to evaluate the influence of this remedy on immunological angiogenesis and granulocytes metabolic activity in Balb/c mice. Mice were fed daily, for seven days, with 5.8 mg of PADMA (calculated from recommended human daily dose) or 0.085 mg (dose in the range of active doses of other herbal extracts studied by us previously). RESULTS: Highly significant increase of newly formed blood vessels number in ex vivo cutaneous lymphocyte-induced angiogenesis test (LIA) after grafting of Balb/c splenocytes from both dosage groups to F1 hybrids (Balb/c × C3H); increase of blood lymphocytes and granulocytes number only in mice fed with lower dose of remedy; and significant suppression of metabolic activity (chemiluminescence test) of blood granulocytes in mice fed with higher dose of PADMA. CONCLUSION: PADMA 28 behaves as a good stimulator of physiological angiogenesis, but for this purpose it should be used in substantially lower doses than recommended by producers for avoiding the deterioration of granulocyte function.