High fish consumption may be associated with lower inflammation, suppressing atherosclerotic CVD (ASCVD). Long sleep duration, as well as short sleep, may contribute to inflammation, thus facilitating ASCVD. This study investigated the overall association between fish consumption, sleep duration and leucocytes count. We conducted a cross-sectional study between April 2019 and March 2020 with a cohort of 8947 apparently healthy participants with no history of ASCVD (average age, 46·9 ± 12·3 years and 59 % males). The average frequency of fish consumption and sleep duration were 2·13 ± 1·26 d/week and 6·0 ± 0·97 h/d. Multivariate linear regression analysis revealed that increased fish consumption was an independent determinant of sleep duration (β = 0·084, P < 0·0001). Additionally, habitual aerobic exercise (β = 0·059, P < 0·0001) or cigarette smoking (β = −0·051, P < 0·0001) and homoeostasis model assessment-insulin resistance (HOMA-IR) (β = −0·039, P = 0·01) were independent determinants of sleep duration. Furthermore, multivariate linear regression analysis identified fish consumption as an independent determinant of leucocytes count (β = −0·091, P < 0·0001). However, a significant U-shaped curve was found between leucocytes count and sleep duration, with 6–7 h of sleep as the low value (P = 0·015). Higher fish consumption may be associated with a lower leucocytes count in the presence of adequate sleep duration and healthy lifestyle behaviors. However, long sleep duration was also related to increased inflammation, even in populations with high fish consumption. Further studies are needed to clarify the causality between these factors.

Zn is an essential nutrient for humans; however, a sensitive biomarker to assess Zn status has not been identified. The objective of this study was to determine the reliability and sensitivity of Zn transporter and metallothionein (MT) genes in peripheral blood mononuclear cells (PBMCs) to Zn exposure ex vivo and to habitual Zn intake in human subjects. In study 1, human PBMCs were cultured for 24 h with 0–50 µm ZnSO4 with or without 5 µm N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), and mRNA expression of SLC30A1-10, SLC39A1-14, MT1 subtypes (A, B, E, F, G, H, L, M and X), MT2A, MT3 and MT4 mRNA was determined. In study 2, fifty-four healthy male and female volunteers (31·9 (sd 13·8) years, BMI 25·7 (sd 2·9) kg/m2) completed a FFQ, blood was collected, PBMCs were isolated and mRNA expression of selected Zn transporters and MT isoforms was determined. Study 1: MT1E, MT1F, MT1G, MT1H, MT1L, MT1M, MT1X, MT2A and SLC30A1 increased with increasing concentrations of Zn and declined with the addition of TPEN. Study 2: Average daily Zn intake was 16·0 (sd 5·3) mg/d (range: 9–31 mg/d), and plasma Zn concentrations were 15·5 (SD 2·8) μmol/l (range 11–23 μmol/l). PBMC MT2A was positively correlated with dietary Zn intake (r 0·306, P = 0·03) and total Zn intake (r 0·382, P < 0·01), whereas plasma Zn was not (P > 0·05 for both). Findings suggest that MT2A mRNA in PBMCs reflects dietary Zn intake in healthy adults and may be a component in determining Zn status.

The relationship between serum Mg and blood cell counts in Chinese adult diabetes or central obesity was assessed by investigating 8163 subjects with China Health and Nutrition Survey (mean age 59⋅6 years, 54⋅9 % men). Participants were classified according to blood Mg (below 0⋅65 mmol/l, or 0⋅66–0⋅94 mmol/l or above 0⋅95 mmol/l), type 2 diabetes (yes/no) and central obesity (yes/no). Leucocytes, erythrocytes, platelets (PLT), Hb and glycated Hb (HbA1c) were determined using standardised methods and conditions. HbAc1, leucocytes and PLT were significantly higher among subjects with central obesity than without central obesity (P < 0⋅05). A significant increase for Hb, erythrocytes, PLT, but not leucocytes, across progressive Mg groups was observed in subjects without diabetes (P < 0⋅05). Hb, erythrocytes and HbAc1 were significantly higher among subjects with higher Mg than in subjects with lower Mg with diabetes (P < 0⋅05). Central obesity disturbed the positive association between PLT count and serum Mg. Type 2 diabetes caused metabolism disorder in serum Mg, blood sugar and blood cell count. Hb, erythrocytes and PLT, but not leucocytes, are positively correlated with serum Mg, but this association is somehow disturbed by type 2 diabetes or central obesity.

American trypanosomiasis is a neglected tropical disease whose spectrum has not been quite understood, including the impact of Trypanosoma cruzi infection on the haematological parameters of different vertebrate hosts. Thus, this study was designed to compare the pattern of haematological changes induced by T. cruzi infection in order to identify possible species-specific differences among taxons. We also aimed at evaluating the use of this parameter as a tool for diagnosis during the acute phase, when symptoms are usually masked. For this purpose, we performed a systematic search on PubMed and Scopus databases to retrieve original studies published until August 2016. Thirty-one studies were selected using Prisma strategy, which were then submitted to data extraction and methodological bias analysis. Half of the studies showed that the number of erythrogram decreased in infected animals, indicating anaemia. In 68.2% of the studies, the total amount of leukogram values increased, suggesting infection. The main methodological limitations were insufficient information for T. cruzi strains identification, inoculation routes and parasitological characterization. Most of the mammalian species analysed showed the same pattern of haematological changes following T. cruzi infection, indicating that haematological parameters might direct the diagnosis of Chagas disease in the initial phase.

The prevalence of type 2 diabetes (T2D) is low in populations with a high fish intake; however prospective studies with fish intake have shown positive, negative or no association between fish intake and the risk for T2D. The aim of this study was to investigate the effects of high intake of lean or fatty fish on glucose tolerance, leucocyte membrane fatty acid composition and leucocyte function in overweight/obese adults. In this randomised clinical trial, sixty-eight healthy overweight/obese participants consumed 750 g/week of either lean or fatty fish as dinners, or were instructed to continue their normal eating habits but to avoid fish intake (control group), for 8 weeks. Energy and macronutrient intake and physical activity were not changed within the groups during the study period. High intake of fatty fish, but not of lean fish, significantly improved glucose regulation 120 min postprandially (P=0·012), but did not affect fasting glucose concentration. A smaller increase in fasting to 120 min postprandial insulin C-peptide concentration was seen after fatty fish intake (P=0·012). Lean fish increased the DHA content in leucocyte membranes (P=0·010), and fatty fish increased the total content of n-3 PUFA (P=0·00016) and reduced the content of n-6 PUFA (P=0·00057) in leucocyte membranes. Lean and fatty fish intake did not affect phagocytosis of bacteria ex vivo. The findings suggest that high intake of fatty fish, but not of lean fish, beneficially affected postprandial glucose regulation in overweight/obese adults, and may therefore prevent or delay the development of T2D in this population.

Enrichment of tissues with ≥20-carbon n-3 PUFA like EPA is associated with positive cardiovascular outcomes. Stearidonic acid (SDA; 18 : 4n-3) and α-linolenic acid (ALA; 18 : 3n-3) are plant-derived dietary n-3 PUFA; however, direct comparisons of their impact on tissue n-3 PUFA content are lacking. Ahiflower® oil extracted from Buglossoides arvensis seeds is the richest known non-genetically modified source of dietary SDA. To investigate the safety and efficacy of dietary Ahiflower oil, a parallel-group, randomised, double-blind, comparator-controlled phase I clinical trial was performed. Diets of healthy subjects (n 40) were supplemented for 28 d with 9·1 g/d of Ahiflower (46 % ALA, 20 % SDA) or flax seed oil (59 % ALA). Blood and urine chemistries, blood lipid profiles, hepatic and renal function tests and haematology were measured as safety parameters. The fatty acid composition of fasting plasma, erythrocytes, polymorphonuclear cells and mononuclear cells were measured at baseline and after 14 and 28 d of supplementation. No clinically significant changes in safety parameters were measured in either group. Tissue ALA and EPA content increased in both groups compared with baseline, but EPA accrual in plasma and in all cell types was greater in the Ahiflower group (time × treatment interactions, P ≤ 0·01). Plasma and mononuclear cell eicosatetraenoic acid (20 : 4n-3) and docosapentaenoic acid (22 : 5n-3) content also increased significantly in the Ahiflower group compared with the flax group. In conclusion, the consumption of Ahiflower oil is safe and is more effective for the enrichment of tissues with 20- and 22-carbon n-3 PUFA than flax seed oil.

DHA is an abundant nutrient from marine lipids: its specific biological effects have been investigated in human volunteers, taking into consideration the dose effects. We report herein that, at dosages below 1 g/d, DHA proved to be effective in lowering blood platelet function and exhibited an ‘antioxidant’ effect. However, this was no longer the case following 1·6 g/d, showing then a U-shape response. The antioxidant effect has been observed in platelets as well as LDL, of which the redox status is assumed to be crucial in their relationship with atherosclerosis. Second, the oxygenated products of DHA, especially protectins produced by lipoxygenases, have been considered for their potential to affect blood platelets and leucocytes. It is concluded that DHA is an interesting nutrient to reduce atherothrombogenesis, possibly through complementary mechanisms involving lipoxygenase products of DHA.

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

Vitamin C is an essential nutrient in humans and must be obtained through the diet. The aim of this study was to determine vitamin C uptake in healthy volunteers after consuming kiwifruit (Actinidia chinensis var. Hort. 16A), and to determine the amount of fruit required to raise plasma vitamin C to ‘healthy’ (i.e. >50 µmol/l) and ‘optimal’ or saturating levels (i.e. >70 µmol/l). Leucocyte and urinary vitamin C levels were also determined. A total of fifteen male university students with below average levels of plasma vitamin C were selected for the study. Weekly fasting blood samples were obtained for a 4-week lead-in period and following supplementation with, sequentially, half, one, two and three Gold kiwifruit per d for 4–6 weeks each, followed by a final 4-week washout period. The results showed that addition of as little as half a kiwifruit per d resulted in a significant increase in plasma vitamin C. However, one kiwifruit per d was required to reach what is considered healthy levels. Increasing the dose of kiwifruit to two per d resulted in further increases in plasma vitamin C levels as well as increased urinary output of the vitamin, indicating that plasma levels were saturating at this dosage. Dividing the participants into high and low vitamin C groups based on their baseline plasma and leucocyte vitamin C levels demonstrated that it is critical to obtain a study population with low initial levels of the vitamin in order to ascertain a consistent effect of supplementation.

The NADPH oxidase enzyme system is the main source of superoxide anions in phagocytic and vascular cells. NADPH oxidase-dependent superoxide generation has been found to be abnormally enhanced in several chronic diseases. Evidence is accumulating that polyphenols may have the potential to improve cardiovascular health, although the mechanism is not fully established. Consumption of concentrated red grape juice, rich in polyphenols, has been recently shown to reduce NADPH oxidase activity in circulating neutrophils from human subjects. In the present work we studied whether red grape juice polyphenols affected NADPH oxidase subunit expression at the transcription level. For this, we used human neutrophils and mononuclear cells from peripheral blood, HL-60-derived neutrophils and the endothelial cell line EA.hy926.Superoxide production was measured with 2′7′-dichlorofluorescein diacetate or lucigenin, mRNA expression by real-time RT-PCR and protein expression by Western blot. Each experiment was performed at least three times. In all cell types tested, red grape juice, dealcoholised red wine and pure polyphenols decreased superoxide anion production. Red grape juice and dealcoholised red wine selectively reduced p47phox, p22phox and gp91phox expression at both mRNA and protein levels, without affecting the expression of p67phox. Pure polyphenols, particularly quercetin, also reduced NADPH oxidase subunit expression, especially p47phox, in all cell types tested. The present results showing that red grape juice polyphenols reduce superoxide anion production provide an alternative mechanism by which consumption of grape derivatives may account for a reduction of oxidative stress associated with cardiovascular and/or inflammatory diseases related to NADPH oxidase superoxide overproduction.

The transmission-blocking monoclonal antibody 13.1, which recognizes the ookinete surface antigen Pbs21 of Plasmodium berghei, and an IgG2a isotype control antibody 26.37 were purified by caprylic acid and ammonium sulphate precipitation. Fab fragments were prepared by papain digestion. IgG but not Fab from antibody 13.1 reduced ookinete formation by P. berghei in culture by as much as 94% at a concentration of 100 μg/ml. There was little difference in antibody efficacy in the range 6·25–400 μg/ml in this assay. The parasite was most sensitive to antibody activity in the first 6–9 h of culture, i.e. the gamete/zygote and early retort stages. Peripheral blood leucocytes (PBL) were essential to achieve maximal inhibition by mAb 13.1 (activity was abrogated totally if PBL were removed). Together the data suggest that one of the mechanisms of action of this antibody is antibody-mediated PBL killing. Phagocytosis of parasites was noted in these experiments in all cultures. We have not attempted in this study to distinguish between Fc-mediated opsonization, as opposed to antibody-dependent cellular cytotoxicity.

The leucocyte responses in peripheral blood and pulmonary airways are described following vaccination of mice with radiation-attenuated parasites, and subsequent challenge with normal parasites. Percutaneous vaccination stimulated a large and sustained expansion of the circulating lymphocyte pool, more marked than after intradermal vaccination with lung schistosomula which induced comparable levels of resistance. Macrophages and lymphocytes infiltrated the pulmonary airways in response to vaccination by both routes, the lymphocytes being particularly abundant after intradermal vaccination. Exposure of mice to an equivalent number of normal cercariae induced an earlier lymphocytosis of short duration; far fewer macrophages and lymphocytes infiltrated the lungs than after vaccination. An intense but transient pulmonary eosinophilia peaked at 3 weeks after primary exposure to either normal or attenuated parasites. Percutaneous challenge of vaccinated mice elicited higher levels of circulating lymphocytes than challenge of unsensitized controls. However, whilst leucocyte numbers of all cell types were still elevated in the airways at challenge as a consequence of vaccination, no further cellular recruitment was observed coincident with parasite elimination. Our data are compatible with the hypothesis that the mechanism of immunity in once-vaccinated mice involves a T lymphocyte-macrophage interaction triggered by antigen release from lung schistosomula.

The impact of immune sera, and peripheral blood cells (PBC) from mice immunized with Plasmodium berghei ookinetes; and of purified immunoglobulin or Fab fragments from anti-Pbs21 monoclonal antibody 13.1, upon establishment of oocyst infections in the mosquito was studied. Infections were initiated either from gametocyte-infected mice, or membrane feeders which contained either gametocytes or mature ookinetes. PBC from ookinete-immunized mice presented with non-immune serum failed to show any transmission-blocking activity. Anti-ookinete serum, intact anti-Pbs21 monoclonal antibody 13.1 or its Fab fragments, all inhibited oocyst formation significantly. When gametocyte-infected mice or gametocytes in membrane feeds were used, inhibition did not directly correlate with antibody concentration. In membrane feeders that contained ookinetes and antibody, concentration-dependent inhibition usually occurred. The efficacy of purified 13.1 IgG was dependent upon the ookinete concentration. The ookinete plasmalemma and cytoplasm were significantly disturbed after 12h in bloodmeals that contained antibody 13.1, but not in the isotype controls. These changes may have caused the observed failure of the ookinete to migrate as rapidly as the controls from the destructive environment of the bloodmeal.

Three strains of male and female mice, CFLP, BALB/c and CBA/ca, were infected i.p. with the tetrathyridia of Mesocestoides corti and examined in groups of 5 at 0, 7, 14, 21, 28 and 42 days post-infection. At post-mortem the numbers of parasites both loose in the peritoneal cavity and in the liver tissue were counted, the livers weighed fresh and sections of liver stained to examine the inflammatory response, encapsulation of the tetrathyridia and for eosinophils, neutrophils, mast cells and plasma cells. BALB/c mice had significantly more parasites loose in the peritoneal cavity than CFLP and CBA/ca mice. Infected livers of all three strains were significantly heavier than control livers; the heaviest livers were those of the CFLP followed by the CBA/ca mice which also showed the greatest rate of weight increase. The tetrathyridia from the peritoneal cavities of the CBA/ca and CFLP mice were covered with a ‘mucilage-like’ substance. Tetrathyridia within the host capsules of the CBA/ca mice contained host cells. There was no strain difference with regard to numbers of tetrathyridia in the liver but male mice harboured significantly more parasites than females. Differences in the numbers of cell types within the liver were detected between the strains but no one strain showed any consistent pattern. There was an overall increase in total white blood counts as well as an increase in the number of eosinophils, monocytes, neutrophils and lymphocytes during the course of the infection.

Postprandial hyperglycaemia is thought to increase inflammation in leucocytes. In the present study, we examined whether sucrose loading in rats with moderate postprandial hyperglycaemia induces the expression of cytokines in peripheral leucocytes and whether these inductions are suppressed by inhibiting postprandial hyperglycaemia with the α-glucosidase inhibitor miglitol. One group of streptozotocin-treated rats and age-matched saline-treated rats were orally administered sucrose only, and another group of streptozotocin-treated rats was administered sucrose with miglitol, at a single daily dose for 4 d, under 4 h fasting conditions. Blood glucose levels at 0, 0·25, 0·5, 1, 2 and 3 h and cytokine mRNA in peripheral leucocytes at 0 and 3 h after sucrose loading on days 1 and 4 from the start of sucrose loading were determined. Streptozotocin-treated rats showed moderate postprandial hyperglycaemia (>2000 mg/l) at 0·25–1 h after sucrose loading on days 1 and 4. Postprandial hyperglycaemia was not observed in the miglitol-treated rats loaded with sucrose. Gene expression levels of IL-1β and TNF-α were higher in the streptozotocin-treated rats at fasting on day 1 than in saline-treated rats. Fasting IL-1β and TNF-α gene expression on day 1 were not only increased at 3 h on the same day of sucrose loading, but was also increased at the fasting period on day 4. These inductions on day 4 by intermittent sucrose administration were inhibited by miglitol. The present results suggest that miglitol decreases postprandial hyperglycaemia and intermittent sucrose-induced expression of the IL-1β and TNF-α genes in rat peripheral leucocytes.

Summary

Background: Leucocytes are a pivotal component of the inflammatory cascade that results in tissue injury in a large group of disorders. Free radical production and endothelial activation promote leucocyte–endothelium interactions via endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) which augment these processes, particularly in the setting of reperfusion injury. Propofol has antioxidant properties which may attenuate the increased expression of these molecules that is observed. Methods: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia, then returned to normoxic conditions. Cells were treated with saline, Diprivan® 5 μg mL−1 or propofol 5 μg mL−1, for 4 h after reoxygenation and were examined for ICAM-1 and VCAM-1 expression. Results: Hypoxia did not increase the expression of ICAM-1/VCAM-1. ICAM-1 expression peaked 12 h after reoxygenation (21.75(0.6) vs. 9.6(1.3), P = 0.02). Propofol, but not Diprivan®, prevented this increase (8.2(2.9) vs. 21.75(0.6), P = 0.009). VCAM-1 expression peaked 24 h after reoxygenation (9.8(0.9) vs. 6.6(0.6), P = 0.03). Propofol and Diprivan® prevented this increase, with no difference between the two treatments observed (4.3(0.3) and 6.4(0.5) vs. 9.8(0.9), P = 0.001, 0.02, respectively). Conclusion: These effects are likely to be attributable to the antioxidant properties of propofol, and suggest that propofol may have a protective role in disorders where free radical mediated injury promotes leucocyte–endothelium adhesive interactions.

Numbers of leucocytes in squirrels with gametocytes of Hepatozoon in their blood (infected) were compared with animals without gametocytes (uninfected). Typical values for leucocytes/mm3 blood in uninfected squirrels were: leucocytes 5·7×103, granulocytes 3·4×103, lymphocytes 2·0×103 and monocytes 0·3×103 cells. Infection caused an increase in monocytes, lymphocytes and granulocytes, and there was a significant positive association between parasitaemia level and numbers of both total leucocytes and monocytes. Infected animals had more uninfected monocytes/mm3 blood than did uninfected animals. The proportions of monocytes were more variable over time in infected animals, but no shift between infected and uninfected status was detected. Transfer of serum from infected squirrels to mice resulted in elevated counts of total blood leucocytes, monocytes and granulocytes, but not of lymphocytes, as compared with controls. Serum from squirrels with high parasitaemias had a more marked effect than serum from squirrels with low parasitaemias. Results indicate an infection-related monocytosis, possibly controlled by cytokines, that increases the number of cells available for invasion by gametocytes, thus enhancing the chances of parasite transmission.

As a result of evidence documenting harmful effects of Zn supplementation on immune function and Cu status, thirty-eight men were recruited onto a Zn supplementation trial. The aim was to examine the effects of chronic Zn supplementation on circulating levels of peripheral blood leucocytes and lymphocyte subsets. Subjects (n 19) took 30 mg Zn/d for 14 weeks followed by 3 mg Cu/d for 8 weeks to counteract adverse effects, if any, of Zn supplementation on immune status resulting from lowered Cu status. A control group (n 19) took placebo supplements for the duration of the trial. Dietary intakes of Zn approximated 10 mg/d. Blood samples, taken throughout the trial, were assessed for full blood profiles and flow cytometric analyses of lymphocyte subsets. Putative indices of Cu status were also examined. Results indicate that there was no effect of Zn supplementation on circulating levels of peripheral blood leucocytes or on lymphocyte subsets. Cu status was also unaltered. Independent of supplement, there appeared to be seasonal variations in selected lymphocyte subsets in both placebo and supplemented groups. Alterations in circulating levels of B cells (cluster of differentiation (CD) 19), memory T cells (CD45RO) and expression of the intracellular adhesion molecule-1 (CD54) on T cells were observed. Findings indicated no adverse effects of Zn supplementation on immune status or Cu status and support the US upper level of Zn tolerance of 40 mg/d. The seasonal variations observed in lymphocyte subsets in the group as a whole could have implications for seasonal variability in the incidence of infectious diseases.

Background and objective Respiratory burst is an essential component of the neutrophil's biocidal function. In vitro, sodium thiopental, isoflurane and lidocaine each inhibit neutrophil respiratory burst. The objectives of this study were (a) to determine the effect of a standard clinical induction/tracheal intubation sequence on neutrophil respiratory burst and (b) to determine the effect of intravenous lidocaine administration during induction of anaesthesia on neutrophil respiratory burst.

Methods Twenty ASA I and II patients, aged 18–60 years, undergoing elective surgery were studied. After induction of anaesthesia [fentanyl (2 μg kg−1), thiopental (4–6 mg kg−1), isoflurane (end-tidal concentration 0.5–1.5%) in nitrous oxide (66%) and oxygen], patients randomly received either lidocaine 1.5 mg kg−1 (group L) or 0.9% saline (group S) prior to tracheal intubation. Neutrophil respiratory burst was measured immediately prior to induction of anaesthesia, immediately before and 1 and 5 min after lidocaine/saline.

Results Neutrophil respiratory burst decreased significantly after induction of anaesthesia in both groups [87.4 ± 8.2% (group L) and 88.5 ± 13.4% (group S) of preinduction level (P < 0.01 both groups)]. After intravenous lidocaine (but not saline) administration, neutrophil respiratory burst returned towards preinduction levels, both before (97.1 ± 23.6%) and after (94.4 ± 16.6%) tracheal intubation.

Conclusion Induction of anaesthesia and tracheal intubation using thiopentone and isoflurane, inhibit neutrophil respiratory burst. This effect may be diminished by the administration of lidocaine.