Differences In Red Blood Cells Research Articles

Clinical Biochemistry and Hematology of the Elusive Sun-Tailed Monkey (Cercopithecus solatus) in Gabon: Inaugural Data From the Only Semifree Ranging Colony in the World

Clinical blood biochemistry and hematology are valuable tools to evaluate health and welfare in many animal species. In order to document the general biology of one of the most poorly known nonhuman primate species, and contribute to its conservation, the clinical blood biochemistry and hematology of the sun-tailed monkey (Cercopithecus solatus Harrisson) was investigated in its range of endemicity in Gabon. Data derived from 26 years of clinical monitoring of the only semicaptive colony of this species in the world, housed at CIRMF (Franceville, Gabon), were analyzed in order to establish reference values of age-sex classes. Consistent with previous reports in other primate species, age and sex significantly affected a number of biochemical and hematological parameters in C. solatus. Hematological analyses demonstrated significant differences in red blood cells, hemoglobin (HB), and hematocrit (HT), with males showing significantly greater values than females. In contrast, neutrophil counts were greater in females. An ontogenetic effect was detected for HB, HT, eosinophil, and monocyte counts, while lymphocytes significantly decreased with age. Biochemical analyses also showed significant differences, with females displaying greater cholesterol and alanine aminotransferase levels. Increase in levels of blood urea and aspartate aminotransferase coupled with decrease in albumin in old individuals suggested declining kidney, liver, and muscle functions with age. Interspecific comparisons were conducted and the effects of the unique semifree-ranging setting on the validity and value of the results presented are discussed. The reference values established will be useful in further ecological, parasitological, and virological studies of the sun-tailed monkey.

190: Racial differences in use and efficacy of prenatal vitamin supplementation during pregnancy

Though the importance of folate supplementation in early pregnancy is well-understood, the clinical factors that affect long-term folate status throughout pregnancy have yet to be adequately defined. This study aims to investigate differences in red blood cell (RBC) folate levels seen with gestational age, ethnicity, and prenatal vitamin use.

Growth performance, hematological and biochemical responses of African catfish (Clarias gariepinus) reared at different stocking densities

African catfish (30.71 ± 0.89 g) were stocked at four different densities of 35, 65, 95 and 125 kg m-3 in 120 L aerated tanks for 60 days, with one and a half tanks of water being renewed daily. The effects of stocking density were examined in growth performance and welfare indicators, such as hematological and biochemical indices. Growth decreased with the increasing stocking density, and there is no significant difference between 35 and 65 kg m-3 treatments. Hematological and biochemical indices, including hemoglobin (Hb), erythrocyte sedimentation rate (ESR), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and the mean corpuscular hemoglobin concentration (MCHC) values, total protein (TP), glucose and total cholesterol (TC) levels, aspartate transaminase (AST), alkaline phosphatase (AP) and lactate dehydrogenase (LDH) activities, serum ion levels and pH, were not affected by the stocking density. Consistent with the result of growth, no significant difference in red blood cell (RBC) count and Hematocrit (Hct) values, alanine transaminase (ALT) activity, albumin (Alb) and triglyceride (TG) levels were observed between 35 and 65 kg m-3 treatments, while some parameters, such as Hct, Alb and ALT, were affected significantly when stocking density increased to 95 kg m-3. Impaired welfare indicators, as well as growth performance, need to be taken into account by husbandry practices to assure that high welfare standards are maintained with increasing profitability. Key words: African catfish, stocking density, growth performance, hematological indices, biochemical indices.

Comparative proteomics reveals deficiency of SLC9A1 (sodium/hydrogen exchanger NHE1) in β‐adducin null red cells

Spherocytosis is one of the most common inherited disorders, yet presents with a wide range of clinical severity. While several genes have been found mutated in patients with spherocytosis, the molecular basis for the variability in severity of haemolytic anaemia is not entirely understood. To identify candidate proteins involved in haemolytic anaemia pathophysiology, we utilized a label-free comparative proteomic approach to detect differences in red blood cells (RBCs) from normal and β-adducin (Add2) knock-out mice. We detected seven proteins that were decreased and 48 proteins that were increased in β-adducin null RBC ghosts. Since haemolytic anaemias are characterized by reticulocytosis, we compared reticulocyte-enriched samples from phenylhydrazine-treated mice with mature RBCs from untreated mice. Among the 48 proteins increased in Add2 knockout RBCs, only 11 were also increased in reticulocytes. Of the proteins decreased in Add2 knockout RBCs, α-adducin showed the greatest intensity difference, followed by SLC9A1, the sodium-hydrogen exchanger previously termed NHE1. We verified these mass spectrometry results by immunoblot. This is the first example of SLC9A1deficiency in haemolytic anaemia and suggests new insights into the mechanisms leading to fragile RBCs.

Study on acute-phase protein changes and their diagnostic values in malignant ovine theileriosis

This study was conducted to assess the pattern of changes and the relative value of acute-phase proteins (APPs) including haptoglobin (Hp), serum amyloid A (SAA), ceruloplasmin and fibrinogen in sheep infected with Theileria lestoquardi. The diseased group comprised 50 sheep, naturally infected with T. lestoquardi, and were divided into three subgroups with different parasitaemia rates ( 4%). As a control group, ten uninfected sheep were also sampled. Blood samples were collected, and all measurements were done using validated methods. There were significant differences in red blood cells (RBC), packed cell volume (PCV), haemoglobin (Hb) and concentrations of Hp, SAA, ceruloplasmin and fibrinogen between healthy sheep and those infected with T. lestoquardi with different parasitaemia rates (P 57.15 μg/ml for SAA, >0.42 g/l for Hp, >0.27 g/l for ceruloplasmin and >3.91 g/l for fibrinogen with corresponding 0.89% sensitivity and 0.98% specificity for SAA, 0.88% sensitivity and 0.65% specificity for Hp, 0.55% sensitivity and 0.96% specificity for ceruloplasmin and 0.65% sensitivity and 0.96% specificity for fibrinogen. In conclusion, measuring SAA with the highest sensitivity, specificity and the area under the curve (AUC) compared to the other APPs is a suitable indicator of inflammatory reactions in Iranian fat-tailed sheep infected with T. lestoquardi.

Evaluation of the resistance of indigenous Iranian cattle to Theileria annulata compared with Holstein cattle by measurement of acute phase proteins

This study was conducted to evaluate the resistance of indigenous cattle against Theileria annulata in comparison with that of Holsteins, through assessment of changes in acute phase proteins. Blood samples were collected from 24 indigenous and 26 Holstein dairy cattle, 2–3 years old, which had become naturally infected with T. annulata. Twenty-five healthy cattle, ten indigenous and 15 Holsteins were selected as a control group. The Theileria-infected group were divided into four subgroups according to their parasitemia rates ( 5%). Measurement of red blood cells (RBCs), packed cell volume (PCV), haemoglobin (Hb), haptoglobin (Hp), serum amyloid A (SAA), ceruloplasmin and fibrinogen were done for all animals using validated methods. Results showed significant differences in RBCs, PCV, Hb and concentrations of Hp, SAA, ceruloplasmin and fibrinogen between healthy cattle and those infected with T. annulata with different parasitemia rates in both breeds (P < 0.05). In both breeds, there was significant negative correlation between parasitemia and RBCs, PCV and Hb (P < 0.05). In contrast, with increasing parasitemia rate, a significant increase in MCV, Hp, SAA, ceruloplasmin and fibrinogen was evident. Iranian indigenous cattle in comparison with Holsteins showed lower parasitemia rate, milder clinical manifestations and significantly lower levels of acute phase proteins including Hp, SAA, ceruloplasmin and fibrinogen (P < 0.05).

Local reference ranges for full blood count and CD4 lymphocyte count testing.

Recent advances in full blood count and CD4 technology, coupled with the changing population demographics of the Gauteng region, have necessitated reevaluation of the reference ranges currently in use. A cross-sectional study of 631 female and 88 male HIV-negative participants from the Gauteng region was performed. Full blood count, automated differential and CD4 count analyses were done using the latest internationally accepted technology. Reference ranges were compiled from the 2.5th and 97.5th percentiles for both male and female participant groups, and gender and ethnic comparisons calculated by non-parametric tests. Results of 41 females were removed from the statistical analysis because their results were suggestive of possible anaemia. Full blood count reference interval comparison confirmed gender-specific differences in red blood cell and platelet parameters. Ethnic-specific differences were found for some red blood cell parameters in the black female cohort. In addition, black males and females both generally had lower neutrophil and higher lymphocyte counts than a combined Asian/Caucasian/coloured ethnic group. Comparison of the currently calculated reference ranges with published data and reference values in use indicated that a separate ethnic-specific reference range should be introduced for the percentage/absolute neutrophil count and percentage lymphocytes. In addition, locally derived reference ranges for red cell distribution width (RDW) and CD4 percentage of lymphocytes should be implemented for routine diagnostic testing.

Study on acute phase proteins (haptoglobin, serum amyloid A, fibrinogen, and ceruloplasmin) changes and their diagnostic values in bovine tropical theileriosis

This study was conducted to assess the pattern of changes and the relative value of acute phase proteins (haptoglobin (Hp), serum amyloid A (SAA), ceruloplasmin and fibrinogen) in bovine tropical theileriosis. The diseased group comprised 50 dairy Holstein cattle, 2-3 years old, naturally infected with Theileria annulata. Infected animals were divided into four subgroups with different parasitemia rates (<1%, 1-3%, 3-5%, >5%). As a control group, 20 uninfected cattle were also sampled. Blood samples were collected and all measurements were done using validated methods. There were significant differences in red blood cells (RBCs), packed cell volume (PCV), hemoglobin (Hb) and concentrations of Hp, SAA, ceruloplasmin and fibrinogen between healthy cattle and those infected with T. annulata with different parasitemia rates (P < 0.05). As the parasitemia rate increased in infected cattle, a significant decrease was observed in RBCs, PCV, and Hb. In contrast, with increase in the parasitemia rate, a significant increase in the mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), Hp, SAA, ceruloplasmin, and fibrinogen was evident. The optimal cut-off point was set by the receiver operating characteristics (ROC) method to >5.68 microg/ml for SAA, >0.16 g/l for Hp, >0.064 g/l for ceruloplasmin and >4.00 g/l for fibrinogen with corresponding 84% sensitivity and 100% specificity for SAA, 76% sensitivity and 100% specificity for Hp, 84% sensitivity and 80% specificity for ceruloplasmin and 40% sensitivity and 100% specificity for fibrinogen. SAA had the highest sensitivity and specificity and was diagnosed to be a suitable indicator of APPs changes in bovine theileriosis.

Comparative Profiling of Red Blood Cells from the Beta-Adducin Knockout Mouse Model of Hemolytic Anemia Using Label Free Differential Proteomics

Inherited hemolytic anemia (spherocytosis or elliptocytosis) is one of the most common inherited diseases. While mild to severe inherited hemolytic anemias can arise from defects in the red blood cell (RBC) membrane skeleton, fundamental questions remain unanswered surrounding the clinical variability of known red blood cell mutations. To identify candidate proteins involved in hemolytic anemia pathophysiology, we utilized a label-free comparative approach to detect differences in RBCs from normal and beta-adducin (ADD2KO) knock-out mice. For each genotype, whole blood was taken from independent biological replicates and RBCs were purified using cellulose acetate chromatography. The isolated RBCs were lysed to generate RBC ghosts whose protein complements were digested with trypsin. For each biological replicate, three replicate runs utilizing 0.5 μg digested protein were performed via microcapillary liquid chromatography coupled with tandem mass spectrometry. Using the recently developed software package CRAWDAD, we detected 7 proteins that were decreased and 31 proteins with a greater abundance in the beta-adducin knock-out RBC ghosts. Differences were detected for previously known membrane skeleton components, including the predicted absence of beta-adducin and decrease in alpha-adducin. The actin binding protein capping protein (actin filament) muscle Z-line alpha 1 was increased along with ankyrin 1, spectrin alpha, tropomyosin, and glycophorin C. Interestingly, differences were also detected for the protein oxidative stress-responsive 1 and the uncharacterized protein C10orf58 which contains a thioredoxin motif. While the protein differences span a broad range of cellular processes, some of the proteins are attractive candidates for modifiers of disease severity. This label free approach is the first demonstration of comprehensively analyzing wild type versus kockout mice that circumvents the need for metabolic or chemical labeling with isotopes. This new approach adds a valuable tool to the list of standard assays for analysis of RBCs in cases of hereditary hemolytic anemia.

Commentary: Health policies in the US: can they increase or decrease the gap between subgroups of the population? The case of folic acid

Effective on January 1, 1998, the Food and Drug Administration (FDA) amended the standards to identify several enriched grain products, bromated flour, vegetable macaroni and vegetable noodle products by requiring folic acid fortication. Specifically, the FDA required that these products be fortified with folic acid levels ranging from 0.43 to 1.4 mg/pound or 95 to 309 mg/100 g of product. Although this requirement affects the entire population, the purpose of this amendment was to ensure that women of childbearing age consume the US Public Health Service recommended daily allowance of at least 0.4 mg (400 mg) of folic acid daily to reduce their risk of having a child with spina bifida or other neural tube defects (NTDs). Spina bifida and anencephaly affect approximately 4000 children in the US prior to the folic acid fortification amendment. However, approximately 1000 of these cases have been prevented with folic acid fortification. As with most conditions in the US, estimates for NTDs vary by race and ethnicity, with Hispanics exhibiting the highest estimates and blacks and Asians the lowest. Moreover, NTDs varies by socioeconomic status defined using income and education with the least educated and those with low income exhibiting the highest estimates. Low folate levels not only affect children in utero, but also evidence suggests that low folate levels are associated with increased prevalence of cancer, cardiovascular disease, physical and mental functioning. Thus, despite the fact that the fortification was targeted to women of childbearing age, the FDA amendment could be a preventive paradox for population health by benefiting everyone. The latter could have implications for health disparities across subgroups of the population if differences exist across the outcomes benefiting from the fortification. Findings from existing studies on folic acid preand post-fortification suggest that there are disparities between groups. For instance, Ford and Bowman showed differences in red blood cell (RBC) folate concentrations between non-Hispanic blacks and nonHispanic whites with the highest differences among those with greater than a high school diploma regardless of gender. Conversely, differences between Mexican Americans and non-Hispanic whites were significant for men with at least 9 years of education and for women at the educational attainment extreme (<9 years of education and more than a high school diploma). Ganji and Kafai showed a decrease in prevalence of low RBC folate between 1988–94 and 1999–2002 across all racial/ ethnic and poverty-income ratio groups. However, nonHispanic blacks continue to exhibit a higher prevalence of low RBC folate through this period. Unlike previous studies examining trends between the preand post-fortification period, Dowd and Aiello focused on investigating the magnitude of the racial/ethnic and socioeconomic status (defined using poverty to income ratio) disparities assessed as absolute and relative differences. Using data from the National Health and Nutrition Examination Surveys (NHANES), Dowd and Aiello examined racial/ethnic and income disparities in folate status in US adults aged 25 years or older before (1991–1994) and after (1999–2002) enactment of the folic acid fortification. They found an increase in relative, but a decrease, in absolute difference before and after the fortification. Non-Hispanic blacks had 1.6 (95% CI: 1.4–1.9) greater odds of having low RBC folate (<362.6 nmol) levels compared with non-Hispanic whites in the pre-fortification period. This estimate was 3.7 (95% CI: 2.8–5.0) in the postfortification period. In the pre-fortification period, individuals in the bottom income quartile had a 1.3 (95% CI: 1.1–1.4) greater odds of having low RBC compared with those in the highest income quartile. Finally, in the post-fortification period, this estimate was 2.1 (95% CI: 1.6–2.7). The corresponding absolute differences were 233 (pre-) and 121 (post-fortification) Department of Health Sciences, Graduate Program in Public Health, Lehman College, CUNY, 250 Bedford Park Boulevard West, Gillet 336, Bronx, NY 10468, USA. E-mail: Luisa.Borrell@lehman.cuny.edu Published by Oxford University Press on behalf of the International Epidemiological Association

Elevated Counts of Circulating Endothelial Microparticles in Pediatric Fabry Patients Decreased after Enzyme Replacement Therapy.

Fabry disease, an X-linked metabolic disorder, is caused by insufficient activity of the lysosomal enzyme alpha galactosidase A (α-gal A). This results in impaired catabolism of glycosphingolipids and their subsequent accumulation (Gb3) leading to endothelial dysfunction. Currently, enzyme replacement therapy (ERT) is the only available specific treatment for patients with Fabry disease. The identification of markers that could serve as indicators of disease severity, prognosis and possible effects of specific therapies is highly desirable. Elevated endothelial cell membrane microparticles in blood have been documented for various diseases with a vascular injury component. Thus, we investigated the presence of endothelial cell membrane derived microparticles (EMPs) in peripheral venous blood samples of 10 pediatric Fabry patients (9 males and 1 female) before they were started on ERT and at the end of 6 and 12 months into the treatment regimen of infusions every other week with agalsidase alfa (Shire Human Genetic Therapies, Cambridge, MA) at 0.2 mg/kg. Both the 6 and 12 month samples were collected 14 days after the last enzyme infusion, thus right before the next infusion. Median age of patients was 12 (range: 10 – 18); renal function, urinary protein excretion, and cardiac function and structure were normal. Carbamazepine or gabapentin were common medications. Patients were stable except for one who suffered recurrent symptomatic and lacunar ischemic strokes. Plasma from healthy age-matched volunteers (Ctrl, n=19) was used for comparison. For EMP analysis, which was done at the same time and blindly, we used a three-color flow cytometric assay (Simak et al, J Thromb Haemost 4, 1296–1302, 2006). The analyzed MPs of 0.3 – 1.0 μm in size (mean 0.45 μm) were sedimented from plasma at 20,000 g. EMPs were identified by antibodies to both endothelial antigen CD105 (endoglin) and the more specific CD144 (VE-cadherin). Annexin V was used to identify MPs exposing phosphatidylserine (PS). Our results demonstrated that CD144+CD105+ EMPs were elevated in Fabry patients prior to ERT (522±177/μL) as compared to the control group (393±190/μL, p=0.031). Similarly, CD144+PS+CD41− EMPs were also significantly elevated in Fabry patients (122±55/μL vs. 83±40/μL, p=0.037). It should be noted that the patient experiencing ischemic strokes was not an outlier. In contrast, there were no significant differences in red blood cell (CD235a+), leukocyte (CD45+) or platelet (CD41a+) MP-counts between Fabry patients and the control group. Interestingly, we found a highly significant decrease (p= 0.004) in EMP-counts after 6 months (406±147/μL) and 12 months (282±112/μL) of ERT (see Fig), while platelet, leukocyte and red blood cell MPs did not change significantly. Our results suggest that ERT may influence the counts of circulating EMPs in pediatric Fabry patients. These finding warrant further studies to elucidate how circulating EMPs may correlate with severity and characteristics of endothelial injury in Fabry disease and whether EMP analysis could be used for monitoring the effects of ERT on endothelial functions. The views of the authors represent a scientific opinion and should not be construed as FDA policy. [Display omitted]

Adhesion of erythrocytes to endothelial cells after acute exercise: differences in red blood cells from juvenile and adult rats

Erythrocytes (RBC) from untrained male Wistar rats and rat glomerular endothelial cells (EC) were used to investigate the effects of acute exercise (speed: 20 m/min, slope: 0, duration: 1 hour) on RBC membrane protein oxidation and adhesion to cultured EC. Experimental animals were divided into juvenile (age 10 weeks) and adult (age 30 weeks) groups for these studies. Immediately following exercise, juvenile rat RBC membrane protein oxidation was significantly enhanced. Adult rat RBC showed significantly higher basal protein oxidation than juvenile RBC; but the level of adult rat RBC membrane protein oxidation was unaffected by exercise. Prior to exercise, adult rat RBC showed significantly higher adhesion to EC than RBC of juvenile rat. There was no difference in plasma fibronectin or fibrinogen levels following exercise. Only juvenile rat RBC showed a significant decrease in sialic acid residue content following exercise. These experiments show that there are changes in RBC-EC interactions following exercise that are influenced by animal age.

Effect of Hematocrit on Exhaled Carbon Monoxide in Healthy Newborn Infants

We tested the hypothesis that, the red blood cell (RBC) mass, estimated by hematocrit (HCT) or hemoglobin (Hb) level, influences the carbon monoxide (CO) production rate. The relationship between end tidal CO corrected for ambient carbon monoxide level (ETCOc) and the RBC mass have been studied in 58 full-term infants at the mean age 4.9 hours. Mean ETCOc was 1.88 ppm (1.3 to 3.4 ppm). ETCOc correlated significantly with HCT (R 2=10.1%, p=0.015) and with Hb (R 2=11%, p=0.011). Infants with a capillary HCT >65% had significantly higher ETCOc (mean 1.99+/-0.49 ppm) than infants with a capillary HCT <65% (1.74+/-0.39 ppm), p=0.035. When CO production was corrected for HCT (ETCOc/HCT), this difference did not longer exist. In newborn infants ETCOc significantly correlates with RBC mass. Comparing different infant's CO generation rate one should take into consideration their initial RBC level. In order to adjust for the existing differences in RBC, we suggest the use of the ETCOc/HCT index.

Influences of Plant Extract Supplementation on Performance and Blood Characteristics in Weaned Pigs

One hundred and twenty crossbred pigs ((Duroc×Yorkshire)×Landrace) were used to determine the effects of plant extract (PE) supplementation on performance and blood characteristics in weaned pigs fed a corn-dried whey-SBM based diet. Treatments were 1) NC (antibiotic free basal diet), 2) PC (NC diet+100 ppm apramycin and 100 ppm oxytetracycline), 3) PE 0.1 (NC diet+0.1% plant extract), 4) PE 0.2 (NC diet+0.2% plant extract) and 5) PE+AB (PC diet+0.1% plant extract). Through the entire experimental period, ADG of pigs fed PC (300 vs. 281 g/d), PE 0.2 (310 vs. 281 g/d) and PE+AB (306 vs. 281 g/d) diets was higher than that of pigs fed NC diet (p<0.05). However, no differences were found among the treatments for ADFI and gain/feed. At day 2 after the onset of the experiment, fecal consistency score of pigs fed PC, PE 0.1, PE 0.2 and PE+AB diets was lower than that of pigs fed NC diet. There were no significant differences in red blood cell, white blood cell, lymphocytes, neutrophils and monocytes concentrations of blood among the treatments. In conclusion, PE can be used to replace antibiotics in diets for weaned pigs without negative affects on performance. Optimal PE levels seemed to be 0.2% and the results obtained point out to a synergic effect of the combination of PE and antibiotic on performance in weaned pigs. (Asian-Aust. J. Anim. Sci. 2004. Vol 17, No. 3 : 374-378)

Influence of reporting error on the relation between blood folate concentrations and reported folic acid–containing dietary supplement use among reproductive-aged women in the United States

Folic acid intake is the most important predictor of blood folate concentrations among nonpregnant women, but the reporting of folic acid-containing supplement use is subject to error. We assessed the effect of reporting error of supplement use on blood folate concentrations. Data from the third National Health and Nutrition Examination Survey were analyzed. Respondents to that survey were asked twice about supplement use: ie, during the household interview, to recall use in the previous month, and during the physical examination, to recall use in the previous 24 h. To examine the effect of error reporting, we classified women (aged 15-44 y) into 5 groups according to supplement use in the previous month (nonusers, those ingesting < 400 micro g/d, and those ingesting >or= 400 micro g/d) and in the 24 h before the physical examination (yes or no). We expected nonappreciable differences in red blood cell (RBC) folate concentration by status of 24-h recall within the same category of previous-month use because RBC folate reflects long-term average consumption. We calculated covariate-adjusted means of serum and RBC folate concentrations. Among women who reported average daily use of >or= 400 micro g folic acid in the previous month, the adjusted mean RBC folate was 436.5 nmol/L (95% CI: 406.7, 466.3 nmol/L) in those who did not take the supplement in the previous 24 h and 519.7 nmol/L (95% CI: 496.2, 543.2 nmol/L) in those who did do so (P < 0.01). This significant difference indicates apparently erroneous reporting of supplement use in the previous month by some participants. The effect of reporting error on blood folate concentrations is important in interpreting survey results, evaluating health education campaigns, and identifying populations needing special education programs.

Uneven changes in circulating blood cell counts with adrenergic stimulation to the canine spleen.

1. Responses of splenic diameter measured by sonomicrometry to alpha- and beta-adrenoceptor stimulants were estimated together with simultaneously measured systemic arterial and splenic venous concentrations of red blood cells (RBC), white blood cells (WBC) and platelets (PLT) in anaesthetized dogs. 2. Intravenous and intrasplenic arterial injections of adrenaline, noradrenaline and phenylephrine all produced profound decreases in splenic diameter. Increases in systemic arterial concentrations of RBC produced by these stimulants were observed immediately following the splenic contraction and marked increases in splenic venous concentration of RBC. 3. Adrenaline and noradrenaline both caused rapid and transient decreases in WBC release from the spleen and these agonists then, in addition to phenylephrine, caused gradual and small increases in systemic arterial WBC concentrations. The increases in arterial RBC and WBC concentrations were abolished by transient isolation of the spleen from the systemic circulation. These three agents did not significantly modify differences between splenic venous and systemic arterial concentrations of PLT. 4. Intra-arterial injections of isoprenaline caused an increase in splenic diameter and a significant decrease in the splenic venous concentration of WBC, but barely influenced the veno-arterial differences in RBC and PLT concentrations across the spleen. 5. The present results indicate that contraction of the spleen through stimulation of splenic alpha1-adrenoceptors contributes to supplying RBC but not PLT into the systemic circulation, whereas splenic beta-adrenoceptor activation leads to splenic dilatation with increased sequestration of WBC to the spleen despite no changes in the release of RBC and PLT from the spleen.

Iron absorption and red blood cell incorporation in premature infants fed an iron-fortified infant formula.

This study was designed to identify differences in red blood cell (RBC) incorporation and iron absorption in premature infants between iron provided in a premature infant formula compared with iron provided as a supplement between feedings. We used a triple stable isotope technique in which 13 infants received 57Fe mixed with Enfamil Premature Formula on d 1 of the study, and 54Fe with a multivitamin supplement between meals on d 2. Two weeks later, blood was drawn for isotope analysis and 58Fe was given i.v. The percentage RBC incorporation of the 54Fe and 57Fe was calculated, and the percent absorption of these tracers was estimated by dividing by the percentage of 58Fe identified in RBCs 14 d after its infusion. We found a small, but significantly greater, percentage of RBC incorporation of the 54Fe given as a supplement compared with the 57Fe given in the formula (9.7 +/- 3.8% versus 7.8 +/- 3.1%, p = 0.02). The RBC 57Fe incorporation was closely correlated with the reticulocyte count (r = 0.80, p = 0.001), but not the serum ferritin or the Hb concentration. Approximately 68% of an i.v. dose of 58Fe was incorporated into RBCs. These findings indicate 1) iron is incorporated well into RBCs from preterm infant formula, with only a small increase in incorporation when given as a supplement, and 2) the reticulocyte count, but not the Hb concentration, is a good measure of RBC iron-incorporating capacity.

Species Differences in Erythrocyte Mechanical Fragility

The erythrocyte destruction rate under constant shear stress was measured to clarify species differences in red blood cell (RBC) mechanical fragility between human, bovine, and ovine cells. Blood was collected from healthy donors by venipuncture. RBC age fractionation was performed by high speed centrifugation (20 min at 12,000 g). Relatively young, middle, and old age RBCs was suspended in Dulbecco's phosphate buffered saline to adjust the hematocrit to 35%. Uniform shear stress was applied to each sample contained in a concavo-convex Couette flow testing machine. Young and old aged samples were exposed to 300 dyne-sec-cm2 for 0 and 15 min. Middle aged samples were exposed to 300 dyne-sec-cm2 for 0, 5, 10 and 15 min. Liberated hemoglobin was estimated by tetramethylbenzidine colorimetric measurement and the erythrocyte destruction rate was calculated. Older samples had a higher hemolysis rate than younger samples in every species. The destruction under constant shear stress is approximately linear in time. Mechanical fragility of ovine and bovine RBCs was 1.8 and 0.5 times as large as human RBCs, respectively. These values could serve as universal standards when extrapolating animal hemolysis data for any blood pump to predict its safety and biocompatibility in human clinical trials.

Ethnic differences in red blood cell sodium/lithium countertransport and metabolic correlates of hypertension: An international collaborative study

Arterial hypertension is frequently associated with metabolic abnormalities. An abnormal activity of the erythrocyte sodium/lithium countertransport (Na/Li CT), an ion transport system under strong genetic control, is also found in people with hypertension and concomitant metabolic abnormalities. However, little information exists with regard to these clinical associations in different racial groups. The aim of this international collaborative study was to investigate Na/Li CT and the metabolic correlates of hypertension in two comparable samples of normotensive and hypertensive populations in the cities of Naples, Italy, and Shanghai, China, using identical, carefully standardized techniques. Blood pressure, anthropometric and metabolic variables, Na/Li CT, and 24-h urinary Na and K excretion were measured in untreated essential hypertensive (HPT) and normotensive (NT) individuals selected by age (35–60 years), body mass index (BMI; < 30 kg/m 2), and blood pressure (BP; HPT, DBP ≥ 95 mm Hg; NT, DBP < 90 mm Hg). The analysis of variance with adjustment for age was used to compare the groups. In the Neapolitan population, hypertensive individuals had higher serum triglyceride ( P < .05) and uric acid levels ( P < .001) than the normotensive group and also had a reduced glucose tolerance ( P < .01) and an enhanced insulin response to the oral glucose tolerance test (OGTT) ( P < .05). No such differences were seen between normotensive and hypertensive Chinese participants. The Neapolitan population (both NT and HPT) had a higher BMI ( P < .01) than their Chinese peers. In the comparison of hypertensive patients in Shanghai and in Naples, the Neapolitans were heavier ( P < .001), had a lower HDL/total cholesterol ratio ( P < .01), an elevated fasting blood glucose ( P < .05), and also a higher glucose ( P < .001) and insulin response ( P < .001) to OGTT. By contrast, they showed a significantly lower urinary Na/K ratio ( P < .001). Na/Li CT was significantly increased in HPT both in Naples (286 ± 24 v 224 ± 13 μmol/L RBC × h; P < .05, M ± SE) and in Shanghai (388 ± 45 v 265 ± 30 μmol/L RBC × h; P < .05). Furthermore, Na/Li CT was significantly and inversely associated with HDL cholesterol both in the Neapolitan ( P < .01) and in the Chinese ( P < .05) population, whereas it was directly correlated with serum triglyceride ( P < .001) and serum uric acid ( P = .001) only in the Neapolitan population. These results indicate that essential hypertension is associated with a higher prevalence of obesity, impaired glucose tolerance, and hyperinsulinemia in Naples than in Shanghai; and Na/Li CT is linked to both high blood pressure and metabolic abnormalities in the Italian sample, whereas it is an isolated marker of hypertension in the Chinese sample.

Clinical assessment of Nafamstat mesilate (FUT-175): a new anticoagulant for immunoadsorption using membrane plasmapheresis (IAP)

Nafamstat mesilate (FUT-175), a new anticoagulant with a short half-life of biological activity, was used in five patients who had a history of bleeding during immunoadsorption using membrane plasmapheresis (IAP) due to excessive heparin. FUT-175 (1.2 mg/kg/h) was injected into the arterial blood line during IAP therapy. The prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time (BT), and complete blood count (CBC) were measured before and after IAP. The PT ( 17.7 ± 0.8 s) after IAP therapy was nearly 1.4 times the level of the PT (12.6 ± 0.6 s) before IAP treatment. The APTT levels after IAP (67.4 ± 2.8 s) were nearly 1.8 times the values before IAP (37.2 ± 2.3 s). There were no significant differences in red blood cell (RBC), hemoglobin (Hb) or platelet counts before and after IAP therapy. No patients developed thrombosis, hemorrhage, or other side effects during IAP. In conclusion, the optimal dosage of FUT-175 was 1.2 mg/kg body wt/h during immunoadsorption with membrane plasmapheresis (IAP). FUT-175 is recommended as a useful anticoagulant during IAP treatment of patients with an increased risk of bleeding.