Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis.

Inflammation has a major impact on iron homeostasis. This review focuses on acute and chronic inflammation as it affects iron trafficking and, as a result, the availability of this essential micronutrient to the host. In situations of microbial infection, not only the host is affected but also the offending microorganisms, which, in general, not only require iron for their own growth but have evolved mechanisms to obtain it from the infected host. Key players in mammalian iron trafficking include several types of cells important to iron acquisition, homeostasis, and hematopoiesis (enterocytes, hepatocytes, macrophages, hematopoietic cells, and in the case of pregnancy, placental syncytiotrophoblast cells) and several forms of chaperone proteins, including, for nonheme iron, the transport protein transferrin and the intracellular iron-storage protein ferritin, and for heme iron, the chaperone proteins haptoglobin and hemopexin. Additional key players are the cell membrane-associated iron transporters, particularly ferroportin (FPN), the only protein known to modulate iron export from cells, and finally, the iron-regulatory hormone hepcidin, which, in addition to having antibacterial activity, regulates the functions of FPN. Interestingly, the impact of infection on iron homeostasis differs among pathogens whose mode of infection is mainly intracellular or extracellular. Understanding how inflammation affects each of these processes may be crucial for understanding how inflammation affects iron status, indicators of iron sufficiency, and iron supplementation during inflammation and how it may potentially result in a beneficial or detrimental impact on the host.

Evaluation of serum protein-based arrival formula and serum protein supplement (Gammulin) on growth, morbidity, and mortality of stressed (transport and cold) male dairy calves.

Previous studies with calves and other species have provided evidence that blood serum-derived proteins and fructooligosaccharides (FOS) may benefit intestinal health. We assessed the effects of supplementing products containing serum proteins as a component of arrival fluid support or serum proteins plus FOS (in addition to additional solids, minerals, and vitamins) in an early life dietary supplement on performance, morbidity, and mortality of stressed (transport, cold) male calves. Male Holstein calves (n=93) <1 wk old were stratified by arrival body weight (BW) and plasma protein concentration, and then randomly assigned to 1 of 4 treatment groups in a 2×2 factorial arrangement of one-time administration of fluid support [either control electrolyte solution (E) or the serum protein-containing arrival formula (AF)] and 14d of either no supplementation (NG) or supplementation with Gammulin (G; APC Inc., Ankeny, IA), which contains serum proteins and FOS in addition to other solids, minerals, and vitamins. Upon arrival at the research facility, calves were orally administered either AF or E. At the next feeding, half of the calves from each fluid support treatment received either milk replacer (20% crude protein, 20% fat) or the same milk replacer supplemented with G (50g/d during the first 14d). Starter and water were freely available. Feed offered and refused was recorded daily. Calf health was assessed by daily assignment of fecal and respiratory scores. Stature measures and BW were determined weekly. Blood samples were obtained at d 0 (before treatments), 2, 7, 14, and 28. Calves were weaned at d 42 and remained in the experiment until d 56. After 2 wk of treatments, calves previously fed AF had greater body length (66.6 vs. 66.0cm), intakes of dry matter (38.7 vs. 23.5g/d) and crude protein (9.2 vs. 5.6g/d) from starter, and cortisol concentration in blood (17.0 vs. 13.9 ng/mL) than calves fed E. Supplementation with G resulted in greater BW gain during the first 2 wk, increased intakes of dry matter and CP, and decreased respiratory scores. For the 8-wk experiment, G supplementation resulted in lower mean fecal score (1.6 vs. 1.8) and fewer antibiotic treatments per calf (1.5 vs. 2.5) than NG. Survival was greater in G than in NG calves (98 vs. 84%). Despite the marked reduction in morbidity and mortality, blood indicators of acute-phase response, urea N, and total protein were not affected by AF or G in transported cold-stressed male calves.

Markers of iron status are associated with stage of pregnancy and acute-phase response, but not with parity among pregnant women in Guinea-Bissau.

While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and α1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27% lower during weeks 16-20 of gestation up to 59% lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52% of the women had sTfR levels >2·3 mg/l, while only 25% had serum ferritin levels 2·3 mg/l decreased to 47% after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 µg/l increased to 33% after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy.

Asymptomatic malaria infection affects the interpretation of biomarkers of iron and vitamin A status, even after adjusting for systemic inflammation, but does not affect plasma zinc concentrations among young children in Burkina Faso.

BACKGROUND: Biomarkers of iron [plasma ferritin (pF)], vitamin A [retinol binding protein (RBP)], and zinc status [plasma zinc (pZn)] are affected by the acute phase response, independent of micronutrient status. OBJECTIVE: The objective of these analyses was to assess how asymptomatic malaria infection affects the interpretation of these biomarkers after adjustment for elevated acute phase proteins (APPs). METHODS: Soluble transferrin receptor (sTfR), pF, RBP, and pZn concentrations were measured among 451 asymptomatic children aged 6-23 mo in Burkina Faso and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or α-1-acid-glycoprotein ≥1 g/L) based on a 4-group categorical model. Plasma histidine-rich protein II (HRP2) concentrations ≥0.75 µg/L were considered indicative of current or recent malaria parasitemia. RESULTS: Of the children in the study, 57.4% had at least 1 elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5 ± 1.5 µg/L vs. 11.1 ± 0.8 µg/L; P < 0.001) and lower RBP (0.79 ± 0.01 µmol/L vs. 0.92 ± 0.01 µmol/L; P < 0.001) than those without, but there were no differences in pZn among those with and without elevated HRP2 (64.9 ± 12.7 µg/dL vs. 64.9 ± 11.1 µg/dL; P = 0.98). Children with elevated HRP2 had higher sTfR than those without (17.6 ± 0.5 mg/L vs. 12.3 ± 0.4 mg/L; P < 0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF < 12 µg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP < 0.84 µmol/L) decreased from 33.4% to 27.7%. CONCLUSIONS: Asymptomatic malaria is associated with indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation. This trial was registered at clinicaltrials.gov as NCT00944853.

Docosahexaenoic acid affects markers of inflammation and muscle damage after eccentric exercise.

The effect of docosahexaenoic acid (DHA) on inflammatory and muscle damage response to acute eccentric exercise and to the subsequent initiation of a resistance training program was studied in 41 untrained men. Subjects consumed either 2 g·d of either DHA or placebo (PL) for 28 days before a 17-day exercise phase (day 1 to day 17) that began with an eccentric exercise bout of the elbow flexors (day 1). For analysis, the exercise period was further divided into an acute response phase (day 1-4). Isometric muscle strength (STR), range of motion (ROM), and delayed onset muscle soreness (DOMS) were measured on days 1, 2, 3, 4, 7, 12, and 17. Fasted blood was measured for interleukin 6 (IL-6), interleukin 1 receptor antagonist, C-reactive protein (CRP), and creatine kinase (CK) on days 1, 2, and 4. Serum CK and CRP were also measured in blood collected on days 7, 12, and 17. In the acute phase, DHA significantly reduced the serum CK (12.5%) and the IL-6 response (32%) but did not affect STR or DOMS. Over the entire 17-day resistance exercise period, DOMS area under the curve was 183.2 ± 96.2 for DHA and 203.2 ± 120.9 for PL (p = 0.054) and the CK response was numerically lower for DHA (p = 0.093). Docosahexaenoic acid supplementation reduced some but not all indicators of muscle damage and inflammation in the 4 days after an acute eccentric exercise bout but did not significantly affect the response to initiation of resistance exercise.

Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves.

Studies in young animals have shown an association between vitamin deficiencies and increased risk of infectious disease; however, there is a paucity of information regarding the effect of acute infection on the vitamin status of the vitamin-replete neonate. To characterize the effects of acute infection on vitamin D and E status of the neonate, 6 vitamin-replete preruminant Holstein bull calves were experimentally infected with bovine viral diarrhea virus (BVDV; strain BVDV2-1373). Six mock-inoculated calves served as controls. Sustained pyrexia, leukopenia, and asynchronous increases in serum haptoglobin and serum amyloid A characterized the response of calves to infection with BVDV. Infection was also associated with increased serum IFN-γ, IL-2, and IL-6 concentrations. During the last 8 d of the 14-d postinoculation period, serum 25-hydroxyvitamin D and α-tocopherol concentrations in infected calves decreased by 51 and 82%, respectively. The observed inverse association between vitamin D and E status and serum amyloid A in infected calves suggests that the infection-induced acute phase response contributed to the reduced vitamin status of these animals. Additional studies are necessary to determine if the negative effect of infection on status are unique to this specific infection model or is representative of preruminant calf's response to acute infection. Studies are also needed to characterize mechanisms underlying infection-related changes in vitamin D and E status and to determine whether additional vitamin D or E supplementation during an acute infection diminishes disease severity and duration in the young animal.

Investigation into the role of Cu/Zn-SOD delivery system on its antioxidant and antiinflammatory activity in rat model of peritonitis.

BACKGROUND: The current study evaluated the role of delivery system (solution, conventional liposomes and PEG-ylated liposomes) on superoxide dismutase (SOD) antioxidant and antiinflammatory properties in a rat model of lipopolysaccharide (LPS)-induced peritonitis. METHODS: Fifty male albino rats (Wistar-Bratislava) were divided into five groups (n=10). Control group received saline and the other four groups received intraperitoneal injections of LPS (5mg/kg). Among the LPS-injected groups, one was LPS control group and the other three groups received the endotoxin injection 30min after receiving the same dose of SOD (500U/kg, ip) in different delivery systems: saline solution (SOD-S), conventional liposomes (SOD-L) or PEG-ylated liposomes (SOD-PL). The animals were euthanized 6h after LPS injection, blood samples were collected and acute phase response (total and differential leukocytes count; tumor necrosis factor α), antioxidants (total antioxidants; reduced glutathione), oxidative stress (total oxidants; lipid peroxidation) and nitrosative stress (nitric oxide metabolites; nitrotyrosine) were evaluated. RESULTS: Intraperitoneal administration of LPS to rats induced a marked inflammatory and oxidative response in plasma. On the other hand, all SOD formulations had protective effect against endotoxin-induced inflammation and oxidative/nitrosative stress, but PEG-ylated liposomes had the most significant activity. Thus, SOD-PL administration significantly reduced the effects of LPS on bone marrow acute phase response, the oxidative status and production of nitric oxide metabolites, while increasing the markers of antioxidant response in a significant manner. CONCLUSION: SOD supplementation interferes both with inflammatory and oxidative pathways involved in LPS-induced acute inflammation, PEG-ylated liposomal formulation being of choice among the tested delivery systems.

The acute phase response affected traditional measures of micronutrient status in rural Zambian children during a randomized, controlled feeding trial.

The acute phase response (APR) to infection can alter blood-based indicators of micronutrient status. Data from a 3-mo randomized, controlled feeding trial in rural Zambian children (n = 181, aged 3-5 y) were used to determine the impact of the APR on indicators of vitamin A and iron status using baseline and final blood samples. Concentrations of acute phase proteins were categorized as raised C-reactive protein (CRP; >5 and >10 mg/L) only, both raised CRP and α1-acid glycoprotein (AGP; >1.2 g/L), raised AGP only, and neither CRP nor AGP raised to identify the respective stages of infection: incubation, early convalescence, convalescence, and healthy state. Data were insufficient to examine the incubation stage of infection. A CRP concentration of >5 mg/L was an effective elevation cutoff point in this population to show impact on micronutrient markers. Time did not affect hemoglobin, serum ferritin, or serum retinol concentrations (P > 0.05). During early convalescence, hemoglobin decreased (14-16%; P ≤ 0.05), serum ferritin increased (279-356%; P ≤ 0.05), and serum retinol decreased (20-30%; P ≤ 0.05). Serum retinol concentrations did not change during convalescence; however, hemoglobin remained depressed (4-9%) and serum ferritin was elevated (67-132%) (both P ≤ 0.05). Modified relative dose response values were unaffected by the APR (P > 0.05) but increased between time points (16%; P ≤ 0.05), indicating a decrease in liver vitamin A reserves on the background of a semiannual vitamin A supplementation program. The observed prevalence of anemia and vitamin A deficiency assessed by serum retinol concentration was higher during the APR (P ≤ 0.05). It is important to consider the impact of infection on dietary interventions and to adjust for acute phase proteins when assessing iron status or vitamin A status by serum retinol concentration alone in children.

Erythrocyte selenium concentration as a marker of selenium status.

BACKGROUND & AIMS: Plasma selenium concentration and glutathione peroxidase (GPx) activity are commonly used as markers of selenium nutritional status. However, plasma selenium concentrations fall independently of selenium status during the acute phase response and GPx is analytically problematic. The assay for erythrocyte selenium is robust and concentrations are unaffected by the systemic inflammatory response. This study was performed to investigate the validity of erythrocyte selenium measurement in assessing selenium status. METHODS: C-reactive protein (CRP), plasma and erythrocyte selenium concentrations and GPx activity were measured in 96 women from two regions of Malawi with low and high selenium dietary intakes. CRP and plasma and erythrocyte selenium was measured in 91 critically ill patients with a systemic inflammatory response. RESULTS & CONCLUSIONS: The median CRP value of all subjects from Malawi was 4.2 mg/L indicating no inflammation. The median CRP value for the critically ill patients was 126 mg/L indicating this group was inflamed. In the non-inflamed population there was a strong positive correlation (r = 0.95) between erythrocyte and plasma selenium and a strong positive correlation (r = 0.77) between erythrocyte selenium and erythrocyte GPx up to 6.10 nmol/g Hb after which maximal activity was reached. In the inflamed population, plasma selenium was low, erythrocyte selenium was normal and there was a weak correlation (r = 0.30) between selenium concentrations in plasma and erythrocytes. This demonstrates that plasma selenium is affected by the inflammatory response while erythrocyte selenium concentration is unaffected and can be used to reliably assess selenium status across a wide range of selenium intakes.

Biological effects of short-term salmon oil administration, using distinct salmon oil sources in healthy dogs.

OBJECTIVES: To assess the short-term effects of feeding distinct salmon oil sources in healthy dogs. METHODS: A diet containing chicken fat as major fat source was fed to 17 dogs for 14 days. For the next 14 days, dogs received one of two diets, both with 1% of chicken fat exchanged for 1% salmon oil; Norwegian or Scottish salmon oil, harvested using a distinct procedure. Finally, all dogs were fed chicken fat again for 14 days. RESULTS: Salmon oil increased serum phospholipid total n-3 polyunsaturated fatty acids, eicosapentaenoic and docosahexaenoic acid and decreased total n-6 polyunsaturated fatty acids and n-6:n-3. The phospholipid fatty acid profile returned to initial values within 2 weeks of discontinuing salmon oil administration. Blood coagulation, acute phase response and plasma immunoglobulin concentrations were not affected by salmon oil and no differences were detected for the measured indices between the two salmon oils. CLINICAL SIGNIFICANCE: Low-dose salmon oil administration alters serum phospholipid fatty acid profile within 2 weeks, but without affecting selected immunologic and coagulation indices. Salmon oil sources from different sources and harvested using a distinct procedure did not induce different effects, most probably because of their similar fatty acid profiles.

Acute phase response of selenium status and glutathione peroxidase activity in blood plasma before and after total knee arthroplasty surgery.

Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p < 0.05) and decreases in the plasma Se concentration (p < 0.05) and in serum albumin (p < 0.05) after surgery were observed. Since albumin is a Se-containing protein and represents a negative acute phase protein that provides amino acids for the production of other series of acute phase proteins, the present results suggest that there is a redistribution of plasma Se to GPx that occurs as an acute phase response, and the source of Se for GPx could be, at least partly, from albumin.

Feeding high proportions of barley grain stimulates an inflammatory response in dairy cows.

The objective of this study was to evaluate effects of feeding increasing proportions of barley grain on acute phase response in lactating dairy cows. Eight cannulated primiparous (60 to 140 d in milk) Holstein dairy cows were assigned to 4 diets in a 4 x 4 Latin square experimental design. The experimental period lasted for 21 d, with 11 d of adaptation and 10 d of measurements. Cows were fed the following diets: 1) no barley grain in the diet, 2) 15% barley grain, 3) 30% barley grain, and 4) 45% barley grain, as well as barley and alfalfa silage and alfalfa hay at 85, 70, 55, and 40% [dry matter (DM) basis]. All cows were supplemented with a 15% concentrate mix. Blood and rumen fluid samples were collected on d 1, 3, 5, 7, and 10 of the measurement period, and pH and endotoxin content were measured in rumen samples. Concentrations of serum amyloid A, lipopolysaccharide-binding protein, haptoglobin, and C-reactive protein in plasma were measured by ELISA. Feeding high proportions of barley grain at 0, 15, 30, and 45% of DM was associated with lower feed intake (32.6, 32.9, 27.34, and 25.18 kg/d +/- 1.30, respectively), lower ruminal pH (6.8, 6.7, 6.7, and 6.5 +/- 0.03, respectively), and higher DM intake (13.33, 15.28, 14.68, and 16.04 +/- 0.63 kg/d, respectively) and milk production (27.2, 28.2, 29.0, and 31.0 +/- 1.2 kg/d, respectively). Ruminal endotoxin increased in cows receiving 30 and 45% barley grain (5,021, and 8,870 +/- 393 ng/mL, respectively) compared with those fed no grain or 15% barley grain (654 and 790 +/- 393 ng/mL, respectively). Plasma concentrations of serum amyloid A, lipopolysaccharide-binding protein, and C-reactive protein increased in cows given higher (30 and 45%) proportions of grain. Plasma haptoglobin was not affected by treatments. In conclusion, feeding dairy cows high proportions (30 and 45% DM basis) of barley grain was associated with lower feed intake and rumen pH, increased endotoxin in the rumen fluid, and stimulation of an inflammatory response.

Differences in stress response between patients undergoing transurethral resection versus endoscopic laser ablation of the prostate for benign prostatic hyperplasia.

The objective of the study was to determine the differences in systemic stress response in patients undergoing transurethral resection of the prostate (TURP) versus endoscopic laser ablation of the prostate (ELAP) for benign prostatic hyperplasia (BPH). The study included 48 patients with BPH (24 treated by TURP and 24 by ELAP). Blood samples were taken from each patient before and immediately after the procedure and on postoperative days 1, 6, and 20, respectively. TURP caused more intense acute-phase response during 24 h after the procedure considering the serum c-reactive protein (CRP) level (p < 0,001) and absolute leukocyte (p = 0.001) and neutrophil number (p = 0.003) in peripheral blood. ELAP caused more decrease in the number of natural killer cells immediately after the procedure (p = 0.048). There were no statistically significant differences between TURP and ELAP procedures in protein and creatine kinase (CK) levels, adrenocorticotropic hormone, and cortisol as well as other immunological parameters. TURP causes more intense acute-phase response than ELAP.

Iron deficiency in the acute-phase reaction after open aortic surgery.

The objective of this study was to quantify the magnitude of iron deficiency in the postoperative period after open aortic surgery. This was a prospective observational study in 55 consecutive patients. Blood samples were obtained on postoperative days 1, 2, 4, 30, and 45, and the parameters determined were the following: iron, transferrin, transferrin saturation index, transferrin-soluble receptor, ferritin, red cell count, hemoglobin, hematocrit, serum C-reactive protein, fibrinogen, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and number of blood units transfused. We performed statistical ANOVA test for repetitive measurements (lower bound) in regard to its basal level. Iron deficiency and its parameters reached the maximum at 48 hours postoperatively (iron: 18.92 g/dL and transferrin saturation index: 11.1%) (P <.05). There was not a complete recovery after 45 days (iron: 51.23 g/dL and transferrin saturation index: 18.0%) (P <.05). A similar evolution was observed in the other measured parameters (red cell count: 3.5 x 106/L.; hemoglobin: 10.4 g/dL; hematocrit: 30.7%) (P <.005), none affecting the values of concentration or volume (P <.05). Transferrin-soluble receptors, normal at first, were increased at postoperative days 30 and 45 (2.7 and 2.4 mg/dL respectively, P <.005). After open aortic surgery there is an important acute-phase reaction, a dramatic iron deficiency, and a lack of its transporters until the 45th analyzed day. The elevation of transferrin-soluble receptors in the 4th and 6th weeks denotes a necessity of iron supplementation for a correct development of the immature hematic cells since blood parameters do not reach normal levels in the 6th postoperative week.

Low serum albumin and the acute phase response predict low serum selenium in HIV-1 infected women.

BACKGROUND: Low serum selenium has been associated with lower CD4 counts and greater mortality among HIV-1-seropositive individuals, but most studies have not controlled for serum albumin and the presence of an acute phase response. METHODS: A cross-sectional study was conducted to evaluate relationships between serum selenium concentrations and CD4 count, plasma viral load, serum albumin, and acute phase response markers among 400 HIV-1-seropositive women. RESULTS: In univariate analyses, lower CD4 count, higher plasma viral load, lower albumin, and the presence of an acute phase response were each significantly associated with lower serum selenium concentrations. In multivariate analyses including all four of these covariates, only albumin remained significantly associated with serum selenium. For each 0.1 g/dl increase in serum albumin, serum selenium increased by 0.8 microg/l (p < 0.001). Women with an acute phase response also had lower serum selenium (by 5.6 microg/l, p = 0.06). CONCLUSION: Serum selenium was independently associated with serum albumin, but not with CD4 count or plasma viral load, in HIV-1-seropositive women. Our findings suggest that associations between lower serum selenium, lower CD4 count, and higher plasma viral load may be related to the frequent occurrence of low serum albumin and the acute phase response among individuals with more advanced HIV-1 infection.

Impact of postoperative shed blood transfusion, with or without leucocyte reduction, on acute-phase response to surgery for total knee replacement.

BACKGROUND: In patients undergoing total knee replacement (TKR) most blood loss occurs postoperatively and return of unwashed filtered shed blood (USB) from postoperative drainage may represent an alternative to allogeneic blood transfusion (ABT). We evaluated the impact of USB return, with or without leucocytes, on the acute-phase response (APR) after TKR. PATIENTS AND METHODS: Forty-eight TKR patients, intended to receive postoperative USB, entered the study. Blood samples were obtained before and 6, 24, 72 h and 7 days after surgery, and from the USB before and after it passed through a 40-microm filter (Group F40) or a leucocyte-reduction filter (Group LRF). Haematimetric parameters, APR proteins (albumin, prealbumin, ceruloplasmin, haptoglobin, C-reactive protein), complement C3 and C4, and cytokines (IL-1beta, IL-6, IL-8, IL-10, and TNF-alpha) were measured in all samples. RESULTS: Twenty-eight patients (Group F40=14, Group LRF=14) received a mean of 1.2 USB units, without any clinically relevant incident, and did not need additional ABT. Sixteen out of the 20 remaining patients who received neither USB nor ABT served as a control group for the postoperative APR study. All patients showed the typical postoperative APR profile and there were no significant differences between groups for APR parameters, postoperative complications, or hospital stay. CONCLUSIONS: Postoperative blood salvage and return, with or without a LRF, after TKR does not present any clinically relevant side-effects and does not modify APR induced by surgery. These findings seem to confirm the clinical experience that postoperative USB return is safe and questions the beneficial effect of using LRF.

Dynamics of antioxidants in patients with acute pancreatitis and in patients operated for colorectal cancer: a clinical study.

OBJECTIVES: This clinical study compared the dynamics of antioxidants levels in patients with acute pancreatitis (AP), patients operated for colorectal cancer (CA), and healthy control subjects. METHODS: This prospective descriptive study enrolled 21 AP and 14 CA patients and 17 healthy controls. Blood was collected from AP patients on days 1, 5, and 9 and from CA patients before surgery and on days 1, 5, and 9 after surgery. We measured concentrations of selenium in plasma, red blood cells (RBCs), and big-toe nails, vitamin A (retinol) in serum, alpha-tocopherol in serum and in RBCs, vitamin C in serum, concentration ratio of 9,11- and 10,12-octadecanoic acids to linoleic acid in RBC membrane, activity of superoxide dismutase, and glutathione peroxidase in RBCs. RESULTS: Plasma concentrations of selenium, vitamin A, and vitamin C were significantly lower in AP and CA patients than in healthy controls over the monitored period (P < 0.05). Patients with severe AP had a significantly lower concentration of selenium in RBCs than did healthy controls and CA patients (P < 0.05). The concentration of selenium in toe nails of AP patients was significantly lower than that in CA patients and healthy controls (P < 0.001). The marker of increased reactive oxygen species activity the ratio of 9,11- and 10,12-octadecanoic acids to linoleic acid in RBCs was significantly higher in AP and CA patients than in healthy controls (P < 0.05). CONCLUSIONS: Low levels of measured antioxidants and increased activity of reactive oxygen species occurred during the course of AP. These findings applied in particular to patients who had severe AP. Levels of measured antioxidants seemed to be similar in AP and CA patients except for lower levels of selenium in toe nails in AP patients and lower selenium concentrations in RBCs in patients with severe AP.

Relationships between serum concentrations of C-reactive protein and micronutrients, in patients with tuberculosis.

Studies on the serum concentrations of micronutrients in tuberculosis (TB), and their relationship to the acute-phase response (APR), are scarce. The serum concentrations of zinc, copper, selenium and vitamins A and E in 46 smear-positive cases of pulmonary TB (PTB) from Ecuador were therefore compared with those in 10 healthy Ecuadorian volunteers, and the correlations between these concentrations and the serum concentration of C-reactive protein (CRP) were evaluated. Compared with the healthy volunteers, the PTB cases had significantly lower serum concentrations of zinc, retinol and selenium and significantly higher serum concentrations of copper. Both groups had moderately high concentrations of selenium in their sera. The PTB cases who had >50 mg CRP/ litre (a concentration indicative of an APR) had lower serum concentrations of retinol and zinc than the cases with lower CRP concentrations. In patients with PTB, hypozincaemia and hyporetinolaemia are strongly associated with the APR. It is therefore necessary to consider the extent of activation of the APR when interpreting serum micronutrient concentrations in patients with TB.

Alpha and gamma tocopherol metabolism in healthy subjects and patients with end-stage renal disease.

BACKGROUND: The metabolism of alpha and gamma tocopherol, the major components of vitamin E, have not been studied in uremic patients. The major pathway of tocopherol metabolism is via phytyl side chain oxidation, leaving carboxyethyl-hydroxychromans (CEHC) as metabolites. Alpha and gamma CEHC are water soluble, renally excreted, with known potent anti-inflammatory and antioxidative properties. METHODS: We examined serum alpha and gamma tocopherol and respective CEHC concentrations in 15 healthy subjects and 15 chronic hemodialysis patients. RESULTS: Serum alpha tocopherol levels were similar in hemodialysis patients (12.03 +/- 1.34 microg/mL) and healthy subjects (11.21 +/- 0.20 microg/mL), while serum gamma tocopherol levels were significantly greater in hemodialysis patients (3.17 +/- 0.37 microg/mL) compared to healthy subjects (1.08 +/- 0.06 microg/mL, P < 0.0001). Serum alpha and gamma CEHC levels were tenfold and sixfold higher in hemodialysis patients compared to healthy subjects, respectively (both P < 0.0001). Serum alpha and gamma tocopherol levels and CEHC metabolites were also measured after supplementation of alpha- or gamma-enriched mixed tocopherols in both hemodialysis patients and healthy subjects. Tocopherol administration resulted in modest or nonsignificant changes in serum tocopherol concentrations, while markedly increasing serum CEHC concentrations in both healthy subjects and hemodialysis patients. Hemodialysis resulted in no change in the serum alpha or gamma tocopherol concentrations while decreasing serum alpha CEHC and gamma CEHC levels by 63% and 53%, respectively (both P = 0.001 versus predialysis). Fourteen-day administration of gamma-enriched but not alpha tocopherols lowered median C-reactive protein (CRP) significantly in hemodialysis patients (4.4 to 2.1 mg/L, P < 0.02). CONCLUSION: First, serum alpha and gamma CEHC accumulate in uremic patients compared to healthy subjects; second, supplementation with tocopherols dramatically increases serum CEHC levels in both healthy subjects and hemodialysis patients; and, finally, CEHC accumulation may mediate anti-inflammatory and antioxidative effects of tocopherols in hemodialysis patients.

Dietary conjugated linoleic acid lowers plasma cholesterol during cholesterol supplementation, but accentuates the atherogenic lipid profile during the acute phase response in hamsters.

Conjugated linoleic acid (CLA) reportedly exerts anticarcinogenic and antiatherosclerotic effects in animals. To test the hypothesis that the putative antiatherosclerotic effect of CLA might derive from an anti-inflammatory or antioxidant action on lipoprotein metabolism, an acute phase response (APR) was elicited in hamsters while varying dietary cholesterol and vitamin E intakes in two experiments. The effect of CLA intake (to 1%) was examined with 0% (Experiment 1, 7 wk) and 0 or 0.3% (Experiment 2, 12 wk) cholesterol, at which point APR was induced. In hamsters not fed dietary cholesterol (Experiment 1), CLA exaggerated the rise in plasma and LDL cholesterol observed during the APR. When CLA was fed concurrently with cholesterol (Experiment 2), plasma and liver cholesterol were reduced up to 40% independent of the APR. In addition, CLA decreased body weight gain and adipose reserves in Experiment 1, but not in Experiment 2. Because CLA failed to attenuate APR and was not influenced by vitamin E status, an antioxidant/anti-inflammatory role was not apparent. However, the reduced burden on liver and lipoprotein cholesterol induced by CLA during cholesterol feeding, suggests that CLA curtailed cholesterol absorption, whereas the rise during APR suggests that CLA exaggerated the impaired clearance of plasma cholesterol associated with acute inflammation.