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Background: Loperamide, a potent opioid, has been used as an in vivo probe to assess P-glycoprotein activity at the blood-brain barrier, because P-glycoprotein inhibition allows loperamide to cross the blood-brain barrier and exert its central opioid effects. In humans, studies with nonselective and moderately potent inhibitors resulted in mild opioid effects but were confounded by the concurrent inhibition of loperamide's metabolism. The authors studied the effect of the highly selective, potent P-glycoprotein inhibitor tariquidar on loperamide's central opioid effects., Methods: In a randomized, double-blind, crossover study, nine healthy subjects received on 2 study days oral loperamide (32 mg) followed by an intravenous infusion of either tariquidar (150 mg) or placebo. Central opioid effects (pupil diameter, sedation) were measured for 12 h, and blood samples were drawn up to 48 h after drug administration to determine plasma loperamide concentrations and ex vivo P-glycoprotein activity in T lymphocytes. Values for pupil diameter and loperamide concentrations were plotted over time, and the areas under the curves on the tariquidar and placebo study day were compared within each subject., Results: Tariquidar did not significantly affect loperamide's central effects (median reduction in pupil diameter area under the curve, 6.9% [interquartile range, -1.4 to 12.1%]; P = 0.11) or plasma loperamide concentrations (P = 0.12) but profoundly inhibited P-glycoprotein in lymphocytes by 93.7% (95% confidence interval, 92.0-95.3%)., Conclusion: These results suggest that despite full inhibition of lymphocyte P-glycoprotein, the selective P-glycoprotein inhibitor tariquidar does not potentiate loperamide's opioid brain effects in humans.

Throughout the annual cycle, demands on competing physiological systems change, and animals must allocate resources to maximize fitness. Immune function is one such system and is important for survival. Yet detailed empirical data tracking immune function over the entire annual cycle are lacking for most wild animals. We measured constitutive immune indices once a month for a year on captive red knots (Calidris canutus). We also examined temperature as an environmental contributor to immune variation by manipulating ambient temperature to vary energy expenditure. To identify relationships among immune indices, we performed principal-component analysis. We found significant repeatability in immune indices over the annual cycle and covariation of immune indices within and among individuals. This covariation suggests immune strategies as individual traits among individuals and the use of different immune strategies during different annual-cycle stages within individuals. Over the annual cycle, both higher-cost phagocyte-based immunity and lower-cost lymphocyte-based immunity were high during mass change, but there was a clear shift toward lower-cost lymphocyte-based immunity during peak molt. Experimental manipulation of temperature had little effect on annual variation in immune function. This suggests that other environmental factors, such as food availability and disease, should also be examined in the future.

Sepsis and associated diseases such as systemic inflammatory response syndrome and multiple organ dysfunction syndrome represent common posttraumatic complications on intensive care units induced by a variety of body defense mechanisms. Natural killer (NK) cells are part of the innate immune system. They are thought to play an important role in the development of such syndromes by interplay with other immune cell types and subsequent activation of the inflammatory cascade. To test this hypothesis, NK cells were depleted by administration of antimouse asialo-GM1 antibody in a murine polytrauma model consisting of femur fracture, hemorrhagic shock, and subsequent sepsis. Mortality and immune parameters such as cytokine expression in lung and liver, lymphocyte phenotyping, lymphocyte apoptosis, and organ pathology were determined 96 h after sepsis induction. Survival values showed 50% in the control sepsis group and 100% after NK cell depletion. Thus, NK cell depletion resulted in 50% mortality reduction. Furthermore, we found reductions in the inflammatory response, represented by IL-6 expression in liver, and a decrease in infiltrating neutrophils in the liver and lung. In addition, lymphocyte apoptosis in spleen was decreased by depletion of NK cells. Taken together, these data demonstrate that NK cells contribute to the pathogenetic pathways in a murine polytrauma model. One main mechanism of action seems to be the induction of systemic inflammatory events. Thus, depletion of NK cells results in attenuated inflammation and an overall improvement in outcome. Therefore, NK cells can be considered as important targets for therapeutic strategies.

The aim of the present study was to determine the association between prenatal stress and immune function in human adults. Peripheral blood mononuclear cells (PBMCs) from 34 healthy young women whose mothers experienced major negative life events during their pregnancy (Prenatal Stress, PS group, mean age 25, SD +/- 4.34 years), and from a female comparison group (n = 28, CG, mean age 24 +/- 3.40 years), were stimulated with phytohemagglutinin (PHA), and subsequent cytokine production was measured. A bias for T-helper 2 (Th2) cytokine production due to an overproduction of IL-4 relative to IFN-gamma after PHA stimulation was observed in PS subjects. In addition, IL-6 and IL-10 were also significantly elevated. To the best of our knowledge, this study is the first to suggest a direct association between prenatal stress exposure and alterations in immune parameters in adult women., ((c) 2008 Wiley Periodicals, Inc.)

E3 ubiquitin ligase Casitas B cell lymphoma-b (Cbl-b) has been recently highlighted as a negative regulator of T-cell activation and which dysfunction usually results in autoimmunity. To present, however, the possible involvement of Cbl-b in multiple sclerosis (MS), an autoimmune demyelinating disease mediated by T-helper 1 (Th1) cells is still unclear. To clarify this, using reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses, we thus investigated the levels of Cbl-b mRNA and protein in peripheral blood T-lymphocytes isolated from 11 MS patients in acute relapse phase and 20 cases in remission phase. 16 healthy subjects were used as normal control. Cbl-b mRNA and protein levels were found both significantly down-regulated in peripheral blood lymphocytes isolated from MS patients (P<0.0001). Interestingly, this decrease of Cbl-b protein but not mRNA levels was significantly more marked in samples of relapsed patients than that of remitted cases (P<0.0001). In addition, it was shown that Cbl-b mRNA levels being inversely correlated with the frequency of MS clinical relapses (P<0.0001). Altogether, the data show for the first time that Cbl-b dynamics in peripheral blood T-lymphocyte subset and which possible relationship with the clinical onsets during MS.

Positive results were attained when human peripheral blood lymphocytes (PBLs) were investigated for their ability to propagate a transmissible cytotoxic activity (TCA) isolated on VERO cell cultures from a sample of cerebrospinal fluid (CSF) drawn from a woman with ischemic brain injury. In consideration of this finding it can be assumed that "in vivo" blood lymphocytes contributed to give rise to the TCA detected "in vitro" in the CSF inoculum.

A 15-year-old boy with systemic lupus erythematosus, who on a follow up visit complained of recurrent episodes of fever, easy fatiguability, and seizures. Investigations revealed lymphocytosis (95%), anemia, and a positive PCR for cytomegalovirus (CMV). Electron microscopy of the lymphocytes revealed intranuclear inclusion bodies supporting the diagnosis of CMV infection. The child was treated with ganciclovir and discharged. At discharge the child was afebrile. However, lymphocytosis persisted even after 9 months of discharge. Repeated screening for possible lymphoreticular malignancy was negative. It is likely that lymphocytosis in this child was due to persistence of CMV infection in host cells leading to continued provocation of the host immune system.

Crotoxin is the main neurotoxic component of Crotalus durissus terrificus snake venom and modulates immune and inflammatory responses, interfering with the activity of leukocytes. In the present work, the effects of crotoxin on the number of blood and lymphatic leukocytes and on lymph nodes and spleen lymphocytes population were investigated. The toxin s.c. administered to male Wistar rats, decreases the number of lymphocytes in blood and lymph circulation and increases the content of B and T-lymphocytes in lymph nodes. These effects were detected 1-2h after treatment. The crotoxin molecule is composed of two subunits, an acidic non-toxic polypeptide, named crotapotin and a toxic basic phospholipase A(2) (PLA(2)). PLA(2), but not crotapotin, decreased the number of circulating blood and lymph lymphocytes. Crotoxin promotes leukocyte adherence to endothelial cells of blood microcirculation and to lymph node high endothelial venules, which might contribute to the drop in the number of circulating lymphocytes. Crotoxin increases expression of the adhesion molecule LFA-1 in lymphocytes. The changes in the expression of the adhesion molecule might contribute, at least in part, for the increased leukocyte adhesion to endothelium. Zileuton, a 5-lipoxygenase inhibitor, blocked the decrease in the number of circulating leukocytes induced by crotoxin and also abolished the changes observed in leukocyte-endothelial interactions, suggesting the involvement of lipoxygenase-derived mediators in the effects of the toxin.

Comparative analysis of results of clinical and laboratory evaluation of patients with chronic nasal or nasal sinuses' diseases (chronic rhinitis or maxillary sinusitis) associated or not associated with Chlamydia infection was performed. It was shown that in patients infected with Chlamydia, along with unidirectional changes typical for all patients irrespective from presence or absence of Chlamydia, the features of immune response against these infectious agents take place.

Mothers can strongly influence the development of their offspring, and if maternal resources are limited, they may influence optimal reproductive strategies. In birds, maternally deposited carotenoids are a prominent component of egg yolk and are vital for the development of the embryo. However, results of long-lasting fitness consequences of this early nutritional environment have been scarce and inconsistent. In addition, sex-biased sensitivity to different egg components is one of the mechanisms postulated to account for sex-linked environmental vulnerability during early life. However, this important aspect is usually not accounted for when investigating maternal investment in carotenoids. In this study we gave carotenoid (lutein) supplements to female Eurasian kestrels (Falco tinnunculus) before and during egg laying. The experiment increased female plasma carotenoids, but this effect was not apparent in hatchling and fledgling plasma carotenoid concentration. Also, results showed that carotenoid supplementation increased the high density lipoprotein to low density lipoprotein ratio in adult females, suggesting that dietary carotenoids may influence lipid metabolism. Furthermore, the effect of the treatment was manifested in several nestling health state parameters. Nestlings of carotenoid-supplemented females were infested by less intestinal parasite groups, had higher lymphocyte concentrations in blood plasma, and were less stressed (heterophile to lymphocyte ratio) than control nestlings. In addition, an interaction between the experimental treatment and nestling sex was apparent for globulin concentrations, favouring the smaller male nestlings. Thereby, suggesting that males benefited more than females from an increase in maternal carotenoid investment. Our study shows that an increase in carotenoids in the maternal diet during egg laying favours nestling development in kestrels, and may also affect nestlings in a sex-specific way.

Macrophage migration inhibitory factor (MIF) has recently been implicated in the pathogenesis of malarial anaemia. However, field studies have reported contradictory results on circulating MIF concentrations in patients with clinically overt Plasmodium falciparum malaria. We determined plasma MIF levels over time in 10 healthy volunteers during experimental P. falciparum infection. Under fully controlled conditions, MIF levels decreased significantly during early blood-stage infection and reached a nadir at day 8 post-infection. A decrease in the number of circulating lymphocytes, which are an important source of MIF production, paralleled the decrease in MIF levels. Monocyte/macrophage counts remained unchanged. At MIF nadir, the anti-inflammatory cytokine interleukin (IL)-10, which is an inhibitor of T-cell MIF production, was detectable in only 2 of 10 volunteers. Plasma concentrations of the pro-inflammatory cytokines IL-8 and IL-1beta were only marginally elevated. We conclude that circulating MIF levels decrease early in blood-stage malaria as a result of the decline in circulating lymphocytes.

Lymphocyte subsets in canine umbilical cord blood were flow cytometrically analyzed and compared with those of the dams' peripheral blood. The proportion of CD3+ T lymphocytes, CD21+CD3- B lymphocytes, and CD3-CD21- non-T non-B lymphocytes in umbilical cord blood was 52.9%, 30.4%, and 16.7%, respectively. T lymphocyte/B lymphocyte ratio was significantly lower in the umbilical cord blood than in the dams' peripheral blood (2.1 +/- 1.4 versus 11.0 +/- 8.1, P < 0.001). In contrast, CD4+ lymphocyte/CD8+ lymphocyte ratio was significantly higher in the umbilical cord blood than in the dams' peripheral blood (7.6 +/- 2.2 versus 1.8 +/- 0.6, P<0.001). These findings clarified the phenotypic characters of canine umbilical cord blood lymphocytes.

Background: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and reproductive and metabolic abnormalities. The potential genetic contributors to PCOS are unclear. We tested the hypothesis that genomic instability (chromosome malsegregation and DNA damage) is increased in PCOS., Methods: Overweight age, weight and BMI-matched women with (n=14) and without (n=16) PCOS (age 34.2+/-6.0 years, weight 90.7+/-14.5 kg, BMI 34.0+/-5.6 kg/m(2), mean+/-S.D.) were assessed for chromosome malsegregation (assessed by X chromosome chromogenic in situ hybridisation) and micronucleus frequency (assessed by the cytokinesis block micronucleus index) in lymphocytes., Results: Women with PCOS had significantly elevated genomic instability as demonstrated by a significantly higher number of binucleated lymphocytes containing micronuclei, total number of micronuclei, a higher proportion of aneuploid X chromosome signals (2:1 X and 3:1 X) and a lower proportion of normal X chromosome segregation signals (2:2 X) in binucleated lymphocytes than women without PCOS. Surrogate measures of insulin resistance positively correlated with the proportion of aneuploid cells (2:1; 3:1 X chromosome signals) and inversely with the proportion of normal cells (2:2 X chromosome signals)., Conclusion: Women with PCOS display increased genomic instability (higher micronuclei and chromosome malsegregation) compared to women without PCOS and this increase may be related to the insulin resistance phenotype.

Background: Spaceflight is associated with increased glucocorticoids and catecholamines, both well-known for their immunosuppressive effects. The objective of this study was to develop a model of spaceflight by using a human centrifuge to reproduce launch and landing G forces along with bed rest to simulate microgravity., Hypothesis: Acute changes in G forces are causal factors in neuroendocrine and immune changes., Methods: Ten subjects underwent realistic launch G-force profiles followed by 16 d of 60 head-down tilt bed rest. At the end of the bed rest, subjects were subjected to realistic landing G-force profiles. Stress hormones and changes in leukocyte and lymphocyte subsets were measured in blood and urine samples over the course of the study., Results: Similar to shorter Shuttle missions (i.e., < or = 9 d), plasma cortisol was significantly decreased at simulated landing while urinary epinephrine was significantly increased. Urinary cortisol was significantly increased after simulated launch. The pattern of leukocyte and lymphocyte changes also mirrored the changes found in shorter 9-d spaceflights., Conclusions: These data suggest a role for both catecholamines and glucocorticoids in mediating changes in leukocyte and lymphocyte subsets during simulated microgravity coupled with hypergravity. Our results were also strikingly similar to those from actual Shuttle missions and support our conclusion that we have developed a model of spaceflight.

The practice of induced molting involves the restriction of light, feed removal and optionally water for 5-14 days. However, there is growing concern regarding feed removal and animal welfare issues. With this in mind, alternative diets have been developed to produce similar molting effects as that of feed deprivation. Alfalfa, which largely consists of insoluble fiber, can be used as a molting diet. In this study, heterophil and lymphocyte counts, serum chemistry, and organ weight parameters were evaluated in hens that were deprived of feed or fed alfalfa during a nine day induced molt. Full-fed hens were used as the control. Blood serum parameters assessed included calcium, magnesium, glucose, total protein, ketone bodies, uric acid, and cholesterol. White blood cells were counted and categorized by cell type. On the ninth day of the trial, the hens were euthanized and the liver, spleen, heart, intestine, pancreas, ovary, oviduct, and kidney were collected and weighed. On day 8 birds molted with alfalfa or by feed deprivation had significantly higher (P<0.05) levels of ketone bodies and cholesterol and lower levels of calcium, and magnesium compared to the full-fed hens while birds molted by feed deprivation exhibited significantly lower levels of uric acid. Birds molted by both methods exhibited significant reductions in ovary, oviduct, liver and pancreas weights and increased spleen weights when compared to the non-molted hens. On days 0, 2, and 6 there were no significant differences (P>0.05) in either heterophil or lymphocyte percentages. However, heterophil percentages were higher in feed withdrawal birds than full-fed birds on day 4 but lymphocyte percentages were higher in full-fed birds compared to feed withdrawal birds. On day 8 of the induced molt lymphocyte percentages were higher from full-fed birds when compared to feed withdrawal birds but no significant differences were detectable for heterophil percentages. Based on reproductive organ weight loss and changes in serum and immunological responses of birds during molt, it appears that alfalfa meal can be an effective molt induction alternative.

Objectives: Epidemiological data indicate that the pregnancies of epileptic women constitute about 1% of all pregnancies. A large group of antiepileptic drugs (AEDs) applied in long-term monotherapy or polytherapy produce toxic metabolites as well as free radicals and reactive oxygen species. The aim of this study was to assess the potential genotoxic effect of AED therapy in pregnancy on DNA structure of umbilical cord blood lymphocytes., Material and Methods: The study group were 30 newborns (14 males and 16 females) of mothers receiving long-term AED therapy during pregnancy. The AED considered were carbamazepine, valproic acid, phenyltriazine, benzodiazepine, gamma-aminobutyric acid and sulfonamide analogues. The controls were infants born to mothers not exposed to any medication in pregnancy (n = 20). Positive controls were the same infants, but in this case Nitrogranulogen (Sigma) was added to the collected cord blood samples (n = 11). Micronucleus (MN) assay was used as an indicator of chromosome damage. The frequency (%) of MN/1000 binucleated cells and the nuclear division index (NDI) were calculated., Results: Mean MN frequency and NDI were respectively 0.110 (+/-0.152), 1.592 (+/-0.206) in the study group and 0.050 (+/-0.061), 1.628 (+/-0.178) in the controls (statistically non-significant difference, p > 0.1)., Conclusion: The findings did not reveal any genotoxic effect or inhibition of nuclear division in cord blood lymphocytes by AED metabolites. This was reflected by the absence of significant between-group differences in the mean MN frequency and NDI.

Bone marrow thymocytes in part mediate the bone-preserving effects of estrogen by decreasing their production of osteoclast growth factors such as interleukin-1 and -6 and tumor necrosis factor alpha in the presence of physiological amounts of estradiol. Although several in vitro studies implicate the T-lymphocyte as a candidate mediator of estrogen signaling in the skeleton, whether these cells or any lymphocytes ordinarily express one or both nuclear estrogen receptors was previously unresolved. The purpose of our investigation was therefore to ascertain, by using real-time PCR, immmunoblotting, and cytometric techniques, if any of the nuclear estrogen receptors could be detected in normal peripheral blood mononuclear cells (PBMNC) collected from healthy volunteers. The results of immunoblotting experiments revealed that both estrogen receptor alpha (ESR1) and beta (ESR2) proteins are expressed in nuclei, but not in the cytoplasm of PBMNC harvested from all of the 15 healthy male and female volunteers (aged 23-50 years) we tested. PBMNCs contained mRNA coding for the two major full-length isoforms of ESR2 and the expression of ESR2 protein was localized within a lymphocyte subpopulation by cytometric analysis. Our data provide further evidence that lymphocytes and monocytes are responsive to estrogen and underscore its importance in modulating the immune response, as well as the vascular and skeletal health of men and women.

Purpose: Nearly 40% of newly diagnosed patients with head and neck cancer are malnourished before treatment begins with many researchers ascribing the malnutrition to a paucity of teeth. We attempted to determine if inadequate numbers of occluding pairs of teeth, rather than mere numbers of teeth, in newly hospitalized, untreated head and neck cancer patients correlates with nutritional status parameters used to identify those at heightened risk for malnutrition-related complications., Patients and Methods: Patients and cancer-free, matched controls were evaluated for malnutrition (body mass index < or = 20 [weight (kg)/height (m2)]), serum albumin < or = 2.7 g/dL, hemoglobin < or = 11.9 g/dL, and total lymphocyte count < or = 1,449/muL), and inadequate numbers of occluding pairs of teeth variably defined as less than 5 "posterior pairs" of occluding teeth or less than 6 or 7 "total pairs" of occluding teeth., Results: Head and neck cancer patients had significantly lower body mass index (P = .005) and total lymphocyte count (P = .019) than controls, but there were no significant correlations between the nutritional and dental variables in either group., Conclusions: Untreated head and neck cancer patients frequently have nutritional status parameters indicating heightened risk for malnutrition-related complications but inadequate masticatory function is not a causative factor.

Immunoglobulin (Ig) of Japanese flounder (Paralichthys olivaceus) was purified by a combination of salting-out and DEAE Sepharose Column chromatography. The purified immunoglobulin had an apparent molecular weight of 74 kDa (heavy chain) and 24 kDa (light chain) in SDS-PAGE. Eighteen hybridomas secreting monoclonal antibodies (MAbs) against Japanese flounder Ig were obtained by immunisation of Balb/C mice with purified Ig preparations, which were selected on the basis of the double indirect enzyme-linked immunosorbent assay (D-ELISA). Two of them designated as 2D8 and 2H1 were cloned by limiting dilution and characterised with western blotting, indirect immunofluorescence assay test (IIFAT) and fluorescence-activated cell sorter (FACS) analysis. Under reducing conditions in western blotting, both MAb 2D8 and MAb 2H1 were specific for the heavy chain of Japanese flounder Ig. MAb 2D8 was used to identify surface Ig-positive lymphocytes in the peripheral blood, spleen and pronephros of healthy Japanese flounder by flow cytometry. FACS analysis revealed that 40.48% of lymphocytes in the peripheral blood, 17.32% in the spleen and 9.67% in the pronephros were reactive to 2D8.

Objective: Resident immune cells are a hallmark of atherosclerotic lesions. The sphingolipid analogue drug FTY720 mediates retrafficking of immune cells and inhibits their homing to inflammatory sites. We have evaluated the effect of FTY720 on atherogenesis and lipid metabolism., Methods and Results: ApoE-/- mice on a normal laboratory diet received oral FTY720 for 12 weeks, which led to a 2.4-fold increase in serum cholesterol (largely VLDL fraction) and a 1.8-fold increase in hepatic HMGCoA reductase mRNA. FTY720 increased plasma sphingosine-1-phosphate and induced marked peripheral blood lymphopenia. A discoordinate modulation of B, T and monocyte cell numbers was found in peripheral lymphoid organs. Overall depletion of T cells was accompanied by a relative (2-fold) increase in regulatory T cell content paralleled by a similar increase in effector memory T cells (CD4+ CD44hi CD62lo) as absolute numbers of both subpopulations remained essentially unchanged. Lymphocyte function was unaltered as indicated by anti-OxLDL antibodies and T cell proliferation. There were no changes in atherosclerotic lesions in early and established atherosclerosis., Conclusions: FTY720 mediated peripheral lymphocyte depletion and retrafficking without altering function and overall balance of pro- and antiatherogenic lymphocyte populations. A net decrease in lymphocyte numbers occurred concomitantly with a more proatherogenic hypercholesterolemia resulting in unaltered atherogenesis.

Purpose: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (gamma-H2AX) foci formation in peripheral blood lymphocytes of cancer patients., Material and Methods: gamma-H2AX formation was quantified as the mean number of foci per lymphocyte (N(meanH2AX)) and the percentage of lymphocytes with > or =n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning., Results: There was a strong linear correlation between the mean number of gamma-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 +/- 0.8 foci Gy(-1), the slopes for brain, upper leg and pelvic sites were significantly shallower by -4.7, -4.3, and -3.8 Gy(-1), respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 +/- 2.6 Gy(-1) (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (-1.5 +/- 0.7 Gy(-1), p = 0.03) later (> or =10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 +/- 0.12 foci per Gy with no evidence of inter-individual heterogeneity., Conclusions: gamma-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered.

Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless, exposure to pesticides represents a potential risk to humans. This paper describes a study of possible genetic damage in the people living in regions contaminated with complex mixture of pesticides in Göksu Delta. In this study, used methods were chromosomal aberration (CA), sister chromatid exchange analysis (SCE) in the peripheral blood lymphocytes, and micronucleus (MN) assay in the buccal epithelial cells. In the present investigation, 32 affected subjects consist of 16 smoking and 16 non-smokings and an equal number of control subjects were assessed for genome damage. Micronucleus (MN), Broken egg (BE), Karyorrhexis (KR), Karyolysis (KL) and Binucleus (BN) frequencies were higher in affected subjects than in controls. Smoking had a statistically significant effect on the Micronucleus, Karyorrhexis and Binucleus frequencies for both the control and the exposed group. Also smoking and exposure affected the frequency of sister chromatid exchange and chromosomal aberrations compared with control groups.

The purpose of this study was to investigate the effects of footbathing on autonomic nerve and immune function. Eleven healthy female volunteers (aged 22-24 years) undertook footbaths at 42 degrees C for 10 min, with or without additional mechanical stimulation (air bubbles and vibration). Autonomic responses were evaluated by electrocardiography and spectral analysis of heart rate variability, and by measurement of blood flow in the sural region. White blood cell (WBC) counts, ratios of lymphocyte subsets, and natural killer (NK) cell cytotoxicity were used as indicators of immune function. Footbathing with mechanical stimulation produced (1) significant changes in the measured autonomic responses, indicating a shift to increased parasympathetic and decreased sympathetic activity and (2) significant increases in WBC count and NK cell cytotoxicity, suggesting an improved immune status. Because these physiological changes are likely to be of benefit to health, our findings support the use of footbathing in nursing practice.

Immune changes following 2 h of intensive cycling with or without rest intervals were measured in trained cyclists (n = 12) who functioned as their own controls during two test sessions that were separated by two weeks. Subjects cycled for 2.0 h at approximately 64 % Watts(max) continuously (C) or with 3-min rest intervals (R) interspersed every 10 min (2.6 h total time), with the order of the sessions randomized. Blood samples were collected 30-min pre-exercise, and immediately and 1-h postexercise, and assayed for blood leukocyte subset counts, plasma IL-6, IL-10, IL-1ra, IL-8, PHA-induced lymphocyte proliferation, and natural killer cell activity (NKCA). Significant time effects were measured for all immune measures, but no significant differences in the pattern of change were found between C and R exercise trials. In conclusion, immune changes induced by 2 h of intense and prolonged exercise paralleled those measured when athletes rested 3 min every 10 min of exercise.

Objective: Although immune dysfunction in patients with cancer could be multifactorial, the immune system may be modulated by nutritional substrates and genetic background. Our study evaluated the effect of G308A polymorphism of the tumor necrosis factor-alpha (TNF-alpha) gene on inflammatory markers in patients after surgery for head and neck cancer who received early enteral nutrition., Methods: A population of 60 patients with oral and laryngeal cancer was enrolled. At surgery patients were treated with a hyperproteic enteral diet. Perioperatively and on postoperative day 6 the following parameters were evaluated: serum values of prealbumin, transferrin, total number of lymphocytes, interleukin-6, TNF-alpha, and C-reactive protein. In addition, genotyping of G308A gene polymorphism was assessed., Results: Patients' mean age was 61.1 +/- 14.6 y (four women, 56 men) with a body mass index of 25.4 +/- 5.2 kg/m(2) and a previous weight loss of 0.35 +/- 0.2 kg. Forty patients (37 men, 3 women; 66.6%) had the genotype G308/G308 (wild group) and 20 patients (19 men, 1 woman; 23.4%) had the genotype G308/A308 (mutant group). A significant increase in prealbumin and transferrin levels was detected in both groups. C-reactive protein decreased in both groups (wild group: 105.1 +/- 60 versus 53.8 +/- 62.3 mg/dL, P < 0.05; mutant group: 99.5 +/- 46 versus 43.9 +/- 51.9 mg/dL, P < 0.05). Interleukin-6 decreased in both groups (wild group: 20.1 +/- 22 versus 6.2 +/- 4.1 pg/mL, P < 0.05; mutant group: 22.3 +/- 38 versus 9.2 +/- 7.4 pg/mL, P = NS). Lymphocytes increased in both groups (wild group: 1102 +/- 468 versus 1600 +/- 537 10(3)/mL, P = NS; mutant group: 1441 +/- 739 10(3)/mL versus 1669 +/- 614 10(6)/mL, P = NS). TNF-alpha showed no changes., Conclusion: The G308A polymorphism of the TNF-alpha gene did not affect levels of inflammatory markers in patients after surgery for head and neck cancer who were treated with early enteral nutrition.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings.

Objective: The benefit of immune-enhancing diets (IEDs) in the intensive care unit remains controversial. Considering their complexity, the role of each component, in particular arginine (Arg), in their properties is largely unknown. The aim of this study was to determine the role of arginine in the immunomodulatory effects of an IED (Crucial) in head-injured rats., Design: Thirty-four rats were randomized into five groups: AL (ad libitum), HI (head-injured), HI-STD (HI + standard enteral nutrition, EN), HI-STD-Arg (HI + standard EN + Arg in equimolar concentration to Arg in IED), and HI-IED (HI + IED). These isocaloric and isonitrogenous diets were administered over 4 days. After death, the thymus was removed and weighed. The density of CD25, CD4 and CD8 on lymphocytes from blood and from Peyer patches was evaluated. Mesenteric lymph nodes, liver and spleen were cultured for analysis of enterobacterial translocation and dissemination., Measurements and Results: HI induced an atrophy of the thymus which was not corrected by the standard diet (HI 0.27 +/- 0.03, HI-STD 0.35 +/- 0.03 vs. AL 0.49 +/- 0.02 g; p < 0.05). However, the standard diet supplemented with arginine limited the thymic atrophy and the IED restored thymus weight. CD25 density and interleukin-2 production were increased only in the HI-STD-Arg and HI-IED groups (p < 0.05). Head injury induced enterobacterial translocation and dissemination which were blunted only in the HI-STD-Arg group (p < 0.05)., Conclusions: In this rat HI model, arginine appears to be safe, contributes to a large extent to the immunomodulatory effects of the IED, and seems to limit enterobacterial translocation and dissemination more efficiently alone than in an IED.

Occupational exposure in copper smelters may produce various adverse health effects including cancer which, according to available epidemiologic data, is associated mainly with exposure to arsenic. Despite a number of well-documented studies reporting an increased risk of cancer among copper smelters workers, the data on genotoxic effects in this industry are scarce. In view of the above, an assessment of micronuclei (MN) frequency in peripheral blood lymphocytes and buccal epithelial cells from copper smelter workers was undertaken. Additionally, the clastogenic/aneugenic effect in lymphocytes was assessed with the fluorescence in situ hybridization (FISH). The study was conducted in three copper smelters in southwestern Poland. The subjects (n = 72) were enrolled among male workers at departments where As concentration in the air was up to at 80 microg/m(3). Exposure was assessed by measurement of arsenic concentration in urine and toenail samples. The control group (n = 83) was recruited from healthy male individuals living in central Poland who did not report any exposure to known genotoxins. The results of our study showed a significant increase in MN frequency in peripheral blood lymphocytes and in buccal epithelial cells of smelter workers, compared to the controls (7.96 +/- 4.28 vs. 3.47 +/- 1.70 and 0.98 +/- 0.76 vs. 0.50 +/- 0.52, respectively). The FISH technique revealed the presence of clastogenic and aneugenic effects in peripheral blood lymphocytes in both groups. The clastogenic effect was slightly more pronounced in the smelter workers; however, the difference was not statistically significant. The mean arsenic concentrations in urine (total arsenic species) and in toenail samples in the exposed group were 54.04 +/- 42.26 microg/l and 7.63 +/- 7.24 microg/g, respectively, being significantly different from control group 11.01 +/- 10.84 microg/l and 0.51 +/- 0.05 microg/g. No correlation between As content in urine or toenail samples and the genotoxic effect was found under study.

Aim: To determine peripheral blood lymphocyte subsets--T cells, helper T cells, cytotoxic T cells, B cells, and natural killer cells, natural killer cell cytotoxicity, serum cortisol concentration, and lymphocyte glucocorticoid receptor expression in Croatian combat veterans diagnosed with chronic posttraumatic stress disorder (PTSD); and to examine the relationship between the assessed parameters and the time passed since the traumatic experience., Methods: Well-characterized group of 38 PTSD patients was compared to a group of 24 healthy civilians. Simultaneous determination of lymphocyte subsets and the expression of intracellular glucocorticoid receptor was performed using three-color flow cytometry. Natural killer cell cytotoxicity was measured by (51)Cr-release assay and the serum cortisol concentration was determined by radioimmunoassay., Results: We found higher lymphocyte counts in PTSD patients than in healthy controls (2294.7+/-678.0/microL vs 1817.2+/-637.0/microL, P=0.007) and a positive correlation between lymphocyte glucocorticoid receptor expression and the number of years that passed from the traumatic experience (r(s)=0.43, P=0.008). Lymphocyte glucocorticoid receptor expression positively correlated with serum cortisol concentration both in PTSD patients (r=0.46, P=0.006) and healthy controls (r=0.46, P=0.035)., Conclusion: This study confirmed that the immune system was affected in the course of chronic PTSD. Our findings also indicated that the hypothalamic-pituitary-adrenal axis profile in PTSD was associated with the duration of the disorder. Due to the lack of power, greater sample sizes are needed to confirm the results of this study.

Three-spined sticklebacks Gasterosteus aculeatus are frequent paratenic hosts of the nematode parasites Anguillicola crassus and Camallanus lacustris. As paratenic hosts, sticklebacks could spread infection by carrying high numbers of infective stages. In contrast, low infective ability of either parasite for the paratenic host could hinder the spread of infection. In the present study, G. aculeatus was, for the first time, infected under controlled laboratory conditions with defined doses of the parasites. Sticklebacks were exposed to 6, 12, 18 and 24 parasite larvae to determine the infective ability of the 2 nematode species. There were significantly higher infection rates for C. lacustris (18 to 49%) than for A. crassus (4 to 14%) at each exposure dose. In C. lacustris-infected sticklebacks, infection rates tended to be highest after exposure to 12 C. lacustris larvae and lowest after exposure to 24 parasites. In A. crassus-infected sticklebacks, no effect of parasite exposure dose on infection rates was observed. Immunity parameters such as respiratory burst activity and lymphocyte proliferation of head kidney leukocytes recorded 18 wk post exposure were not significantly affected by either parasite or exposure dose. Granulocyte:lymphocyte ratios were elevated only within the stickleback group showing the highest infection intensity of C. lacustris, i.e. to those exposed 18 parasites.

This longitudinal, prospective study sought to establish whether pediatric Crohn's disease (CD) and ulcerative colitis (UC) are associated with increased levels of cytogenetic damage and whether folate supplementation in combination with other treatments mitigates cytogenetic damage in children with inflammatory bowel disease (IBD). After a 1-mo treatment and folate supplementation, all clinical tests in CD (n = 24) and UC (n = 17) patients improved. Patients with CD were comparable in the cytogenetic response with controls (n = 28) assessed by micronucleus (MN) assay, but both groups differed from the UC group. While the MN frequency in epithelial cells slightly decreased from first to second observations in CD patients (p = 0.05) and controls (p = 0.11), an increase was observed in UC patients (p = 0.001). Similar changes were observed in blood lymphocytes resulting in significantly higher levels of the MNs and chromosome bridges in UC patients. These preliminary findings of a difference in chromosome damage between pediatric UC patients compared with CD patients and healthy controls warrant confirmation and expansion to determine (1) the role of cytogenetic damage in the pathogenesis of these diseases, (2) relative contribution of treatment and folate supplementation, and (3) potential links to the eventual development of cancer in some patients.

Lymphocyte numbers in the blood are used to evaluate the immune status on a daily basis in medicine. Several studies have documented the normal ranges of lymphocytes and lymphocyte subsets in the peripheral blood. A variety of techniques and criteria have revealed clear differences between the lymphocyte subsets in childhood and adolescence. Race and gender are also variables for blood lymphocytes, and even environmental factors seem to influence the numbers of some lymphocyte populations. However, do all these variations in lymphocyte subsets in the peripheral blood mirror changes in the lymphocyte populations of the whole body, or is it just a result of different migratory habits of cells? The factors influencing the distribution of lymphocytes in the peripheral blood with regard to the different abilities of T and B cells to migrate to distinct lymphoid or non-lymphoid tissue are summarized. In addition it will be described how the removal of organs (e.g. thymus, spleen, liver) influences the distribution of lymphocytes in the blood. All these parameters should be considered not only in the clinical situation when the immune status of a patient is extrapolated from the lymphocyte numbers in the blood, but also when interpreting treatment effects in patients.

Menopause is often accompanied with weight gain, metabolic lipid abnormalities, and oxidative stress. In this study, we investigated the combined effects of exercise and soy isoflavone supplementation on the lipid profiles and antioxidant capacities of ovariectomized rats. Twenty-five female Sprague-Dawley rats were divided into 5 groups: sham-operated, ovariectomized (OVX), OVX with exercise (OVX+EX), OVX with soy isoflavone supplementation (OVX+ISO), and OVX with both soy isoflavones and exercise (OVX+ISO+EX). After 12 weeks of intervention, antioxidant status was evaluated in collected blood samples by the ferric reducing ability of plasma (FRAP), glutathione (GSH) content, and sodium oxide dismutase (SOD) activity. DNA damage in the lymphocytes was determined using alkaline single-cell gel electrophoresis (the Comet assay). Although there were no significant differences in weight gain and food intake, weight gain was lower in OVX+EX, OVX+ISO, and OVX+ISO+EX than in OVX. OVX+EX, OVX+ISO, and OVX+ ISO+EX showed a significant decrease in total cholesterol, triglycerides, and LDL-cholesterol compared to OVX. The soy isoflavone supplemented group had significantly increased FRAP values and GSH contents in contrast to no changes in the exercised group, whereas exercise markedly increased SOD activity and H2O2-induced DNA tail length and tail moment. Exercise with soy isoflavone supplementation significantly increased FRAP values and had no difference on SOD activity, including DNA damage. These results demonstrate that a combined treatment of moderate exercise and soy isoflavone supplementation could exert a beneficial effect on weight control and lipid profiles, and offer protection from exercise-induced oxidative stress in postmenopausal women.

Limited proteolysis of multiple intracellular proteins by endogenous Ca-dependent cysteine proteases--calpains--is an important regulatory mechanism for cell proliferation, apoptosis etc. Its importance for cellular functions is stressed by existence of endogenous calpain inhibitors--calpastatins. The calpain-calpastatin system within living cells is in a fragile balance, which depends on both partners. The interdependence of calpain--a protease--and calpastatin--an endogenous inhibitor and at the same time a substrate for this enzyme makes any assessment of actual activity of this enzyme in the cells very difficult. In this work we made an attempt to estimate and compare the activity of calpain in human peripheral blood lymphocytes by assessing the levels of limited proteolysis of calpastatin in these cells by western blot, while at the same time the levels of calpain protein inside these cells was measured by flow cytometry. Our results indicate that it is possible to compare (semi-quantitatively) the activities of calpain in peripheral blood CD4+ and CD19+ lymphocytes from various donors that way. Preliminary results showed that calpain activity is increased in the CD4+ T cells isolated from peripheral blood of rheumatoid arthritis patients as compared to control lymphocytes. Extremely high intrinsic activity of calpain was detected in chronic lymphocytic leukemia (CD19+) cells. All this confirms the detection of immunoreactive products of calpastatin as a good maker of endogenous calpain activity.

The purpose of this study was to evaluate the feasibility of measuring stress hormones and immunity following rape. The long-term goal is to evaluate the predictive value of stress-immune-inflammatory responses to later health outcomes. Fifteen women reporting rape were compared with 16 control participants. Serum stress hormones, proinflammatory cytokines, acute phase proteins, functional assays, and lymphocyte subsets were measured in blood samples. Women reporting rape had higher cytotoxic cells, lower B lymphocyte counts, higher proinflammatory biomarkers, and decreased lymphocyte proliferation compared to the control group. This finding suggests that rape produces activation of the innate immunity and suppression of some aspects of adaptive immunity. If these immune changes persist, they may contribute to the pathophysiology of long-term health sequelae by provoking chronic inflammation and decreased cellular immunocompetence.

Dendritic cells (DC) are the most potent antigen-presenting cells (APC) and are pivotal for initiating allograft immunity. Recently, particular DC subsets have been implicated also in allogeneic T cell hyporesponsiveness. Alemtuzumab (anti-CD52, Campath-1H) is a novel T cell depleting antibody that is currently under investigation for the use in allogeneic organ transplantation. While recent studies demonstrated a conspicuous effect of alemtuzumab on peripheral DC in clinical graft-versus-host disease, its efficiency in patients receiving allogeneic organ transplants is still undefined. In the present study we assessed the peripheral DC repertoire in kidney transplant recipients after either alemtuzumab induction therapy followed by FK506 monotherapy or after conventional immunosuppression (FK506, mycophenolate mofetil and steroids) without any induction agent. Induction with alemtuzumab caused a strong and sustained reduction of the total number of peripheral DC and a significant shift from myeloid to plasmacytoid DC subsets (mDC/pDC ratio) as early as 1 month post-transplantation. These data show that alemtuzumab induction targets the peripheral DC repertoire, which might add another mechanism allowing immunosuppressive drug minimization. Further studies are warranted to further elucidate the functional significance of these finding in the setting of allogeneic organ transplantation.

In the presented study the influence of stress and environmental factors on selected haematological and blood-chemical parameters in racing pigeons was examined. Blood was taken at three defined days and haematological as well as blood-chemical parameters of clinical relevance were determined. In comparison to reference values published for pigeons, the majority of the values obtained in this study were within physiological borders. The daily handling of the pigeons did not have any significant effect on the examined parameters. Also the heterophile/lymphocyte ratio did not show any changes characteristic of a stress reaction. In contrast, after change of the housing dies with pigeons originating normally from a flock, the first blood sampling should be performed after a 4 or 5-day lasting period of acclimatisation to the the individual housing conditions.

Type 2 diabetes mellitus is associated with increased oxidative stress. Free radicals produced during this stress may damage various cellular components. Gliclazide, a second-generation sulfonylurea, is an oral hypoglycemic drug that possesses antioxidant properties. Therefore, gliclazide may diminish the harmful consequences of oxidative stress in diabetic patients. The aim of our study was to evaluate the action of gliclazide on DNA damage and repair in normal human peripheral blood lymphocytes and insulinoma mouse cells (beta-TC-6). DNA damage and repair were induced by hydrogen peroxide, gamma and ultraviolet radiation and MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) in the presence or absence of gliclazide and were analysed by the alkaline comet assay. DNA double-strand breaks were assayed by pulsed-field gel electrophoresis. Gliclazide protected DNA of both kinds of cells from DNA damage induced by chemicals and radiations. These results suggest that gliclazide may diminish the risk of free radical-related diseases associated with type 2 diabetes mellitus and possibly cancer.

A complex situation of chemical exposure has been described in México in a zone that is in transition from rural activities towards intensive industrialization, which has brought environmental pollution: chloroform, methylene chloride, indigo and toluene are some of the pollutants found in the Atoyac and Xochiac rivers. A biomonitoring study was planned in order to establish whether there was a biological effect due to the environmental situation. Communities where leukaemia and thrombocytopenic purpura cases have been reported were included in the study, as well as other communities where such cases have not been described. Three occupations were distinguished, according to chemical exposure: industrial workers, agricultural workers and workers in households, education and commerce. A comprehensive analysis in the micronucleus (MN) test was used to study genotoxicity biomarkers. Two metabolic polymorphisms were determined, namely, glutathione transferase mu1 (GSTM1) and theta1 (GSTT1), which are relevant when oxidative responses are involved. Increased genotoxic damage was found, including cells with >1 MN, >1 chromatin bud, and nucleoplasmic bridges. The genotoxic damage was differentially distributed in the regions studied, being more affected those that are closer to the Atoyac and Xochiac rivers, indicating an effect due to environmental exposure to the contaminants present in the rivers. Further characterization of the exposure regimes in these communities will be done in order to contribute to the alleviation of the health risks that environmental pollution is posing on the inhabitants of this area.

Objective: The authors tested the effect of blood sampling (skin versus venous puncture) on some biochemical and hematological blood parameters in athletes to answer whether skin puncture could be used as a substitute for venous puncture., Design: Comparative study of 2 methods of blood samples collection., Setting: The blood was collected in the same athletes at 3 different moments of the preparatory training phase., Participants: Fourteen male indoor soccer players (22 +/- 1 years old) and 7 female handball players (18 +/- 1 years old) participated., Main Outcome Measurement: Blood was collected in heparin and K3EDTA by Vacutainer BD or Microvette Sarstedt system for biochemical and hematological analyses, respectively., Results: There were no significant statistical differences between the 2 methods for the values of creatine kinase, urea, creatinine, lymphocytes, and platelets. The other hematological analyzes and uric acid exhibited significant higher values in skin blood, although they were all within the normal expected range. A high degree of correlation was observed between the 2 techniques for all parameters., Conclusions: Skin puncture is a reliable, easy, accurate, and less invasive sampling method for assessing hematological and some biochemical parameters in athletes, respecting that blood samples should always be obtained from the same site, especially in follow-up studies.

A rapidly growing body of data suggests that abnormalities in serotonergic function might be involved in the pathophysiology of schizophrenia and that serotonergic mechanisms play a role in the therapeutic effects of antipsychotics. The activity of the serotonin transporter (5-HTT), as determined by [(3)H]5-HT uptake to blood lymphocytes, was measured in 38 medicated schizophrenia patients (15 of them treated with typical antipsychotics and 23 treated with atypical antipsychotics) and 15 healthy control subjects. In addition, the pharmacodynamic characteristics of platelet 5-HTT were assessed by [(3)H]citalopram binding. There were no significant differences in the density (B(max)) of platelet [(3)H]citalopram binding sites between the three groups. Similarly, the dissociation constant (K(d)) values were indistinguishable. There were no significant differences in the maximal uptake velocity (V(max)) of [(3)H]5-HT to fresh lymphocytes between the three groups. The affinity (K(m)) values of 5-HT to the 5-HTT were significantly higher in schizophrenia patients treated with typical antipsychotics compared with control subjects. The K(m) values in schizophrenia patients treated with atypical antipsychotics were significantly lower compared with those observed in the group of schizophrenia patients treated with typical antipsychotics; however, they were comparable to values in the control group. The high values of K(m) associated with typical antipsychotic treatment may be relevant to the high risk of developing extrapyramidal side effects (EPS). The role of the various components of the serotonergic system in the etiopathology of schizophrenia and the mechanisms by which antipsychotics achieve their therapeutic effects need to be further evaluated.

1. A stock of cross-bred CD hens was divided into 'resistant' (R) and 'sensitive' (S) to stress on the basis of the heterophil/lymphocyte (H/L) ratio using the lower 99% confidence limit method for selection. A first generation was produced from these R and S females mated with similarly selected R and S local Barred males. The association between 'resistance' and some production traits was investigated. 2. The proportions of R:S among CD females and Barred males was 51.2:48.8 and 52:48, respectively. Mean H/L ratios for Barred males and females, respectively, were 0.87 +/- 0.03 and 0.83 +/- 0.03 (P > 0.05). 3. Compared with the S group in CD females, the R group had greater egg production (59% vs 51%), egg weight (65.5 g vs 62.6 g) and body weight at 39 weeks (115 g heavier). 4. The superiority of R in terms of proportion of fertile eggs, hatchability and the proportion hatched from those set amounted to 4.8, 6.1 and 5.4%, respectively. 5. The proportion of dead embryos in the R group (5.4%) was lower than in the S group (9.3%). 6. With the F1 generation the R chicks were heavier at hatching. 7. Percentage mortality of male F1 chicks, from hatching to 4 weeks and from 4 to 8 weeks, was lower in the R group. A similar, but non-significant, trend was noted for R females. 8. The progeny of the R group was heavier than the S progeny at 4 and 8 weeks and also the percentage dressed weight of males was greater at 8 weeks. The R group was heavier than the S group at 4, 8 and 12 weeks. 9. These results suggest that selection for general 'resistance', on the basis of the H/L ratio using the 99% lower confidence limit method of selection, is positively correlated with several important production and reproduction traits. Establishing resistant lines with high production rates seems feasible.

Efforts to identify an easy and convenient biomarker of carcinogenesis with potentials of application in mass screening program continue. In a series of investigations on mice exposed to different carcinogens, poly-ADP-ribosylation (PAR) of cellular proteins of different tissues has been shown to be a potential biomarker of carcinogenesis. Because blood based biomarker of carcinogenesis offers significant advantage in its use in a cancer screening program, this investigation was undertaken to find correlations between initiation of carcinogenesis and PAR of bone marrow cell (BMC) and blood lymphocyte (BL) proteins in mice chronically exposed to low dose of dimethylnitrosamine (DMN) for up to four weeks in vivo. The exposure was either alone or in combination with 3-aminobenzamide (3-AB), an inhibitor of PAR. Total PAR of cellular proteins and of histone H1 protein were monitored by slot and Western blot immunoprobe assays, respectively. The PAR of total cellular proteins as well as of histone H1 was down-regulated in duration of exposure dependent manners. The results suggest that BMC and BL mirrored status of PAR in other tissues. This finding opens up the possibility of using PAR as a biomarker of carcinogenesis in a blood based test utilizing immunoprobe assay of cellular PAR.

Problem: Uterine infections often develop in some livestock species during the first luteal phase postpartum. Exogenous prostaglandin F(2alpha) (PGF(2alpha)) induces luteolysis, reduces progesterone, and enables the uterus to resolve infections. However, the effects of PGF(2alpha) on luteal function and on immune functions are confounded. These effects must be disentangled to determine whether alternatives to antibiotic treatments can be successfully developed., Method of Study: Treatments were in a 2 x 2 x 2 factorial arrangement. Main effects were ovariectomy or sham on day 0 (i.e. estrus), exogenous progesterone or sesame oil from day 0 to 11, and exogenous PGF(2alpha) or saline on day 9. Intrauterine inoculations with Arcanobacterium pyogenes and Escherichia coli were administered on day 6., Results: Ewes treated with exogenous PGF(2alpha) either did not have uterine infections, infections were less severe, or infections were resolving when uteri were examined on day 12, despite increased progesterone., Conclusions: Exogenous PGF(2alpha) has effects on the resolution of uterine infections that are independent of its effects on luteal progesterone production.

Background: In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. In this study, immunologic alterations in patients with SAP were analyzed, and immunologic parameters related to infectious complications were clarified., Methods: A total of 101 patients with SAP were analyzed retrospectively. Various immunologic parameters on admission were analyzed and compared between the infection group and noninfection group during SAP. Furthermore, chronologic change in the lymphocyte count was investigated, and its utility for predicting infection was compared with conventional scoring systems., Results: Serum immunoglobulin G (IgG), serum IgM, lymphokine-activated killer cell activity, and natural killer cell activity were low, and the incidence of abnormally low values was 50.0%, 65.0%, 45.5%, and 42.4%, respectively. Serum complement factor 3 was significantly negatively correlated with the APACHE II score. The lymphocyte count was decreased below the normal range, and was significantly negatively correlated with the APACHE II score. CD4-, CD8-, and CD20-positive lymphocyte counts were below the normal range, and CD4- and CD8-positive lymphocyte counts were significantly lower in the infection group. The lymphocyte count on day 14 after admission was significantly lower in the infection group and was more useful for predicting infection than conventional scoring systems., Conclusions: Immunosuppression occurs from the early phase in SAP, and quantitative impairment of lymphocytes, mainly T lymphocytes, may be closely related to infectious complications during SAP. CD4- and CD8-positive lymphocyte counts on admission and the lymphocyte count on day 14 after admission may be useful for predicting infection.

The aim of this study was to analyze background levels of DNA damage in young (19-31 years) non-smoking individuals and to correlate damage to gender and life style. DNA single strand breaks (SSB) and alkali labile sites (ALS) were measured in 99 subjects living in Stockholm, Sweden. Further, oxidative DNA damage was analyzed using the DNA repair glycosylase FPG as well as HPLC-ECD for specific analysis of 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG). We found that males had higher (P < 0.001) levels of SSB + ALS than females, but no difference was seen for oxidative lesions. There was no correlation between FPG sites and 8-oxodG. For females, there was a positive correlation between FPG levels and body mass index and a negative correlation between SSB + ALS and fruit intake. We conclude that the background level of oxidative DNA damage, analyzed with improved methods, is low and that gender, fruit intake and BMI can affect DNA damage.

The present study was carried out to examine the effect of vitamin (V) or trace mineral (TM) mix removal from finisher diet (42-56 d of age) on performance and immunocompetence of broilers. The dietary treatments were: (1) the basal diet with no supplemental V or TM; (2) the basal diet fortified with V mix only; (3) the basal diet fortified with TM mix only; and (4) the basal diet fortified with V and TM mix. At 47 d, four birds from each replicate (20/treatment) were injected with Newcastle disease (ND) antigen and blood samples were collected just before and 9 d after immunisation. The results showed that V and TM mix withdrawal from finisher diet did not impair either weight gain or feed conversion efficiency from d 42 to 56. Feed intake was significantly increased when both mixes were omitted from the diet. Dietary treatments had no effect on carcase yield or proportion of breast and thigh meat and abdominal fat deposition. Packed cell volume (PCV) significantly decreased as a consequence of removal of V, TM and V+TM. Neither heterophil:lymphocyte ratio (H:L ratio), haemagglutination inhibition (HI) nor total antibody titre measured by ELISA were influenced by removal of V or TM supplements. In conclusion, the results from this study suggest that 14-d withdrawal of V or TM mix did not influence the immunocompetence of broilers.

Celiac disease (CD) is a chronic, immune-mediated disorder of the gut, driven by T cells reacting locally to a distinct antigen, gliadin. Thus, CD offers the opportunity to study the T cell memory response to gliadin and whether gut tropism and T helper cell type 1 (Th1) polarization, which characterize the effector phase, are preserved in the memory progeny. It is notable that previous studies yielded conflicting results as to the presence of gliadin-specific memory CD4+ T cells in the peripheral blood of CD patients. However, we used a different and highly sensitive approach based on fluorescein-derived label dilution, whereby the memory cells are identified operationally by their greater capacity to proliferate upon re-encounter with antigen. Thus, using flow cytometry, we could resolve multiple successive generations as well as immunophenotype the dividing cells. Here, we show that the peripheral blood lymphocyte of some CD patients on a gliadin-free diet, but not healthy donors, contains a detectable population of CD4+ memory T cells specific for deamidated gliadin. Moreover, these gliadin-specific memory T cells are marked by a distinctive phenotype: They express high levels of the gut-homing beta7 integrins and primarily produce interferon-gamma and tumor necrosis factor alpha. We conclude that memory for gliadin-derived antigens within the circulating CD4+ T cells is linked with gut tropism as well as Th1 polarization.