Higher Mean Corpuscular Hemoglobin Concentration Research Articles

Hemocytometric Measures Predict the Efficacy of Oral Rehydration for Children with Postural Tachycardia Syndrome

To explore whether hemocytometric measures could be qualified predictors for the effect of oral rehydration salts (ORS) in children with postural tachycardia syndrome (POTS). Thirty-five children with POTS and 29 healthy children were enrolled. General information, hemodynamic status, and baseline hemocytometric variables were collected. Children with POTS received ORS therapy and were followed up for 3 months. The independent risk factors of developing POTS were explored. A receiver-operating characteristic curve was used to evaluate predictive value of hemocytometric variables for therapeutic effectiveness of ORS therapy. Children with POTS had larger mean corpuscular volume (MCV) and lower mean corpuscular hemoglobin concentration (MCHC) values than controls (P < .05). The baseline MCV values positively correlated with heart rate elevation from supine to upright (r = 0.294, P < .05). Both larger MCV and lower MCHC values were independent risk factors of developing POTS (for MCV, P < .05, OR 1.222; for MCHC, P < .05, OR 0.936). In children with POTS, responders to ORS had baseline lower MCV and higher MCHC than nonresponders (P < .05). The receiver-operating characteristic curve for the predictive value of MCHC showed that area under the curve was 0.73. MCHC values could be used to predict the effectiveness of ORS for treating POTS in children.

Abstract 12550: Persistent Relative Hypochromia is Associated With Adverse Outcomes in Non-anemic Patients With Heart Failure

Background: We previously reported that functional iron deficiency, assessed by low mean corpuscular hemoglobin concentration (MCHC), has been associated with adverse outcomes in non-anemic patients with HF. Yet, the effect of change in MCHC levels on outcomes has not been studied before. Methods: We prospectively enrolled 1,579 subjects with HF undergoing coronary angiography, with 5-year follow-up. Blood indices [hemoglobin (Hb), MCHC, MCV, RDW] were assessed on enrollment and after 6 months of follow up by reviewing medical records. Anemia was defined as Hb levels &lt;12 g/dL in males, and &lt;11 g/dL in females. Results: In our population (age 66 ± 10 years, male 65%, CAD 75%), most patients were non-anemic (n=1,161, 73.5%). In non-anemic patients, mean Hb and median (IQR) MCHC were 13.3±1.2 g/dL and 34.2 (33.43-34.9) g/dL, respectively. Non-anemic HF patients with lower MCHC had higher mortality risk [Q1 vs Q4 Hazard ratio (HR) (95%CI) of 2.5(1.9-3.2), p&lt;0.001]. Total of 552 (35%) had follow up Hb levels with a mean time between baseline and follow up levels of 169.3 ± 41.6 days. HF severity (EF, BNP), outcomes and blood indices were similar in patients with and without follow up levels, suggesting good representation of the total population. Changes in MCHC levels was studied in non-anemic patients on baseline and follow up (n=318). Most patient with low MCHC at baseline (&lt;Q1, n=79) continued to have low MCHC on follow up (n=61), while half of the patients with high baseline MCHC (≥Q1, n=239) developed low MCHC on follow up (n=120). In comparison to patient with persistently high MCHC, patients with persistently low MCHC had a significantly increased mortality risk [HR(95%CI) of 3.5(2.1-6.1), p&lt;0.001]. All models remained significant even after adjusting for traditional CAD risk factors, EF and baseline blood indices. Conclusion: Relative hypochromia is an independent predictor of increase mortality in patients with HF, even in the setting of normal hemoglobin levels.

Chronic diclofenac (DCF) exposure alters both enzymatic and haematological profile of African catfish, Clarias gariepinus

Pharmaceuticals are used extensively in human and veterinary medicine to eradicate or prevent diseases. The residues of these drugs have been detected in aquatic ecosystem; nevertheless, their toxicological effects on Clarias gariepinus have not been critically investigated. In this study, the toxic effects of diclofenac (DCF), a non-steroid anti-inflammatory drug, were studied in C. gariepinus by acute and chronic static renewable bioassay. The 96 h LC50 of DCF to C. gariepinus was 25.12 mg/L. Exposure to acute toxicity resulted in abnormal behavior and mortality of some fish. Compared with the control, chronic exposure of the fish to concentration (1.57, 3.14 and 6.28 mg/L) showed significantly higher mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and white blood cell (WBC), with significantly lower haemoglobin (Hb), haematocrit, red blood cell (RBC) and mean corpuscular haemoglobin (MCH) with increase in the concentration of the drug. Furthermore, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and glucose values significantly increased while protein levels were reduced (p < 0.05) in serum and gills throughout the 42-day exposure period. The study reports that DCF-induced enzymatic and haematological changes in the fish and recommends that these parameters be used as potential biomarkers for assessing residual pharmaceuticals available in aquatic ecosystem.

A retrospective study of 1,098 blood samples with anemia from adult cats: frequency, classification, and association with serum creatinine concentration.

BackgroundFrequency and classification of anemia in terms of regeneration status and erythrocyte indices are not well described in cats.ObjectiveTo determine frequency and regenerative status of anemia in samples from adult cats, to assess the sensitivity and specificity of macrocytosis and hypochromasia for detecting regenerative anemia (RA), and to evaluate the association of anemia with increased serum creatinine concentration (SC).Study PopulationLaboratory records from 30,503 blood samples from cats (2003–2011).MethodsClinicopathologic data reviewed retrospectively. Anemia defined as hematocrit (Ht) ≤27%, red blood cell count (RBC) ≤5.5 × 106/μL and hemoglobin (Hb) ≤9.0 g/dL. RA defined by manual absolute reticulocyte count >50 × 103/μL. Macrocytosis was defined as mean corpuscular volume (MCV) >55 fL and hypochromasia as mean corpuscular hemoglobin concentration (MCHC) <31 g/dL. Cutoff for increased serum creatinine concentration was 1.6 mg/dL.ResultsOverall, 1,098 of 30,503 blood samples (3.6%) from cats fulfilled criteria for anemia, 633 of 1,098 (57.7%) classified as nonregenerative (NRA) and 465 of 1,098 (42.3%) as regenerative. RBC, Ht, and Hb were significantly lower in the RA compared to NRA group (P < .05). Sensitivity and specificity of the combined high MCV and low MCHC to detect samples with RA were 19.5 and 90.7%. SC was increased in 572 of the 1,098 anemic samples (52.1%) and in 11,121 of 29,405 of nonanemic samples (37.8%).Conclusions and Clinical ImportanceMajority of anemic samples were classified as NRA. Anemia was more severe in cats with RA. Erythrocyte indices were not sensitive indicators of RA.

Effect of azadirachtin on haematological and biochemical parameters of Argulus-infested goldfish Carassius auratus (Linn. 1758)

Argulosis hampers aquaculture production and alters the host physiology and growth. Azadirachtin is recognized as a potential antiparasitic agent against Argulus sp. The present study aimed to investigate the effect of different concentration of azadirachtin solution on haematological and serum biochemical parameters of Argulus-infested goldfish Carassius auratus. Ninety Argulus-infested goldfish were randomly divided into six equal groups. Fish of group 1-5 were treated with azadirachtin solution through bath of 1, 5, 10, 15 and 20 mg L(-1) as T1, T2, T3, T4 and T5, respectively, and group 6 was exposed to 2% DMSO solution without azadirachtin and considered as negative control T0(-). Along with six treatment groups, a positive control T0(+) of healthy goldfish free from Argulus infestation was also maintained. Parasitic mortality was evaluated after 3 days of consecutive bath treatment. After 7 days of post-treatment, the blood and serum were drawn from each of the treatment groups and haematological and serum biochemical parameters were evaluated. Total leucocyte count (TLC), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), blood glucose, total protein (TP), globulin, serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) were significantly (p < 0.05) high in negative control group when compared with positive control group. It could be concluded that Argulus infestation altered marked haematological and serum biochemical parameters. However, in treated groups complete elimination of Argulus was found in T4 and T5 groups. Also significant (p < 0.05) reduction in haematological and serum biochemical parameters of all the treatment groups were recorded in comparison with negative control group. In addition, T4 and T5 groups showed significantly (p < 0.05) high superoxide dismutase (SOD), catalase, total erythrocyte count (TEC) and haemoglobin (Hb). However, higher mean corpuscular haemoglobin concentration (MCHC), blood glucose and lactate dehydrogenase (LDH) levels in T5 group revealed that higher concentration of azadirachtin have notable effects on activity of vital tissues function and physiology of the host. Argulus spp. from infested goldfish could be eliminated using bath treatment with solution of azadirachtin having concentration of 15 mg L(-1) and that also shifted haematological and serum biochemical parameters towards homeostasis.

Anti-Sports Anaemia Effects of Verbascoside and Martynoside in Mice

This paper aims to investigate the effects of verbascoside and martynoside isolated from PEDICULARIS DOLICHOCYMBA on sports anaemia. Forty mice were divided into four groups: Group R (control group, nonsupplemented and maintained at rest), Group E (nonsupplemented and undergoing exercise), Group VE (supplemented with verbascoside 10 mg/kg per day and undergoing exercise), and Group ME (supplemented with martynoside 10 mg/kg per day and undergoing exercise). After 5 weeks intensive swimming exercises, we measured the RBC count, the hemoglobin concentration, the hematocrit (Hct), the mean corpuscular hemoglobin concentration (MCHC) and the mean corpuscular hemoglobin (MCH). We studied the shapes of RBC and measured the plasma malonyldialdehyde (MDA). We found Group E showed lower RBC, hemoglobin and Hct levels, higher MCHC, MCH, plasma MDA levels and the abnormally shaped RBCs percentage than Groups R, VE and ME. Group ME showed lower RBC and Hct levels, higher MCH, plasma MDA levels and the abnormally shaped RBCs percentage than Group VE. The results indicated that verbascoside and martynoside have the potential of antagonizing sports anaemia, the mechanism of this effect might be related to preventing RBC from free radical damage. Moreover, verbascoside was found to be more active than martynoside.

Critical evaluation of peripheral smear in cases of anemia with high mean corpuscular hemoglobin concentration in children: A series of four cases

Mean corpuscular hemoglobin concentration (MCHC), a parameter that is reported as a part of a standard complete blood count by automated analyzer, is a measure of the concentration of hemoglobin in a given volume of packed red blood cell. Values of MCHC significantly above reference range are not physiologically possible due to limitations on solubility of hemoglobin. The high MCHC can give us a clue to certain type of hemolytic anemia and necessitate critical evaluation of peripheral smear to reach a definitive diagnosis. Here we are presenting a series of four cases with raised MCHC, emphasizing the importance of systematic and meticulous examination of the peripheral smear to render a definitive diagnosis.

K-Cl cotransport modulation by intracellular Mg in erythrocytes from mice bred for low and high Mg levels.

Mg is an important determinant of erythrocyte cation transport system(s) activity. We investigated cation transport in erythrocytes from mice bred for high (MGH) and low (MGL) Mg levels in erythrocytes and plasma. We found that K-Cl cotransport activity was higher in MGL than in MGH erythrocytes, and this could explain their higher mean corpuscular hemoglobin concentration, median density, and reduced cell K content. Although mouse KCC1 protein abundance was comparable in MGL and MGH erythrocytes, activities of Src family tyrosine kinases were higher in MGH than in MGL erythrocytes. In contrast, protein phosphatase (PP) isoform 1 alpha (PP1 alpha) enzymatic activity, which has been suggested to play a positive regulatory role in K-Cl cotransport, was lower in MGH than in MGL erythrocytes. Additionally, we found that the Src family kinase c-Fgr tyrosine phosphorylates PP1 alpha in vitro. These findings suggest that in vivo downregulation of K-Cl cotransport activity by Mg is mediated by enhanced Src family kinase activity, leading to inhibition of the K-Cl cotransport stimulator PP1.

Hematological and serum chemistry profiles of free-ranging southern two-toed sloths in French Guiana.

Free-ranging southern two-toed sloths (Choloepus didactylus) were translocated during the flooding of a forest at a hydroelectric dam site in French Guiana. Over an 11 mo period blood samples were collected from 90 sloths (38 males, 52 females) in order to determine hematological and serum chemistry reference values. Mean values and range of values were calculated for 13 hematological and 21 serum chemistry parameters. Variations associated with sex, age and reproductive status were identified. Males had a significantly lower red blood cell count than females. Immature animals had more monocytes while adults had more neutrophils and higher mean corpuscular hemoglobin concentration. Aspartate aminotransferase and triglyceride values were higher in young than in adult sloths but uric acid was lower. Lactating females showed lower red blood cells count and iron levels than non-lactating females. These profiles will help to provide reliable baseline data for medical evaluation of sloths.

Pulmonary entrapment of sickle cells: the role of regional alveolar hypoxia.

Pulmonary microvascular occlusion by abnormally adherent and/or nondeformable sickle red blood cells (SS cells) may contribute to the pathogenesis of acute chest syndrome of sickle cell disease. We hypothesized that regional alveolar hypoxia reduces SS cell deformability and, by causing regional vasoconstriction, slows regional perfusion, facilitating endothelial adhesion and mechanical entrapment of cells. In isolated rat lungs perfused at constant average flow with physiological salt solution, we separately ventilated the two lungs: one with 95% O2 and the other with 0, 2.5, 5, or 21% O2. We infused a bolus of 99mTc-labeled SS cells or normal human AA cells along with 113Sn-labeled 15-mu m microspheres as a perfusion marker, then sliced the lungs and counted 99mTc and 113Sn. Weight-normalized perfusion decreased with hypoxia (P < 0.02). Retention of AA cells (perfusion-normalized) averaged approximately 1% in lungs ventilated with 95% O2 and increased only twofold with 0% O2. In contrast, retention of SS cells averaged 3-fold higher than that of AA cells at 95 and 5% O2, 15-fold higher at 2.5% O2, and 25-fold higher at 0% O2 (P < 0.01). Histological examination demonstrated entrapment of individual SS cells in alveolar capillaries of hypoxic but not well-oxygenated lungs. Relief of hypoxia, but not increased perfusate flow, caused prompt efflux of most entrapped cells, which were primarily high-density (high mean corpuscular hemoglobin concentration) cells. Thus substantial retention of SS cells does not occur without hypoxia, but regional hypoxia and/or the resulting vasoconstriction causes extraordinary regional retention of dense SS cells, a phenomenon that appears to be due more to mechanical entrapment of nondeformable cells in capillaries than to endothelial adhesion.

Genetic control of erythrocyte volume regulation: effect of a single gene (rol) on cation metabolism.

In laboratory mice we previously defined a gene, rol (resistance to osmotic lysis), based on its effect on erythrocyte osmotic fragility. Here we report a physiological characterization of rol gene action utilizing congenic strains developed for the purpose; these two strains have a common genetic background and differ only by the two alleles of rol, susceptible (rols) or resistant (rolr). In comparison to rols/s erythrocytes, rolr/r cells have a reduced mean cell volume, a higher mean corpuscular hemoglobin concentration and hemolytic volume, and respond differently to swelling induced by ion influx. Rolr/r erythrocytes also have reduced cell water and K, which are associated with a threefold higher activity of the Na-K-Cl cotransporter (measured as ouabain-resistant, bumetanide-sensitive 86Rb influx) and 30% higher Na pump activity. Apart from differences in ion transport and water content, the content of 2,3-diphosphoglycerate (2,3-DPG) in rolr/r cells is 15% lower than in rols/s ones. Analyses of membrane structural components revealed no rol-associated differences in their phospholipid or fatty acid content, nor were strain differences evident among the membrane and cytoskeletal proteins and their posttranslational modifications (phosphorylation and fatty acylation). Rol is not the structural gene for either the alpha- or the beta-chain of hemoglobin and has no effect on erythrocyte production or destruction. The concerted effect of rol variation on erythrocyte volume, water and cation content, cation cotransport, and 2,3-DPG levels is similar in many ways to the variation observed among individual humans for the same characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesion of Sickle Cells to Vascular Endothelium Is Critically Dependent on Changes in Density and Shape of the Cells

Experiments were performed to explore whether adhesion differences among different density sickle (SS) cells are mainly caused by deformability characteristics attendant to density variations, which could affect their surface contacts with the endothelium, or caused by any changes in their membrane surface (eg, receptors). Also, what is the contribution of morphologic attributes of SS cells in adhesive and obstructive events? To resolve these issues, controlled modifications of cell density were performed using Nystatin and sucrose. This allowed elevation of the mean corpuscular hemoglobin concentration (MCHC) of light-density SS2 discocytes to that of SS4 native dense cells, as well as its normalization in both native and artificially dehydrated cells. Hemodynamic and adhesive characteristics of these individual SS cell populations and their defined mixtures were investigated in the ex vivo mesocecum vasculature. Dehydrated (high MCHC) SS2 discocytes, alone or with SS2 control cells, caused a higher peripheral resistance but no persistent microvascular blockage. Nevertheless, dehydrated SS2 discocytes resulted in a significantly decreased adhesion in venules (adhesion sites). Rehydration of these high MCHC discocytes completely restored their adhesivity, similar to that of SS2 control cells. In contrast, irreversibly sickled cell (ISC)-rich SS4 dense cell class (dense discocytes and 66% to 72% ISCs) was less adherent than dehydrated SS2 discocytes, but caused a persistent blockage of small diameter postcapillary venules when infused with SS2 control or dehydrated discocytes. In the areas of adhesion, SS4 dense discocytes outnumbered ISCs by 4 to 1, demonstrating that ISCs, because of their shape characteristics, are minimally adherent but play a distinct role in postcapillary obstruction. When MCHC (density) of SS4 cells was decreased by rehydration, it resulted in an almost complete reversal of their hemodynamic and adhesive behavior, confirming a profound influence of cell density. These findings demonstrate for the first time that, under shear flow, adhesion of different density SS cells to the endothelium is dependent on the inverse of cell density rather than any changes in their adhesion potential. Finally, the trapping of ISC-rich native dense cells, but not of dehydrated discocytes, in the areas of adhesion shows a distinct contribution of ISC in adhesion-initiated vasoocclusion.

Causal role of dense microspherocytes in the anemia of hereditary spherocytosis: Clinical importance of filterability measurements through 3-μm pores

through the 3-llm pore nickel mesh compared with that through the 5-llm pores. It is, therefore, likely that the impaired deformability of HS RBCs arises from the decrease in the cell surface area to volume ratio and the high mean corpuscular hemoglobin concentration. After splenectomy, the dense microspherocytes disappeared, and there was a marked improvement in RBC filterability through 3-llm pores. This suggests that dense cells were microspherocytes that received splenic conditioning in the walls of splenic sinuses. Correspondingly, splenectomy markedly improved clinical manifestations and ameliorated hemolysis. Thus, the laboratory measurement (i.e., the 3-llm filtration test) reflected the patient's clinical state. The use of

Normative Distribution of Complete Blood Count from Early Childhood through Adolescence: The Bogalusa Heart Study

Background. Noting the distribution of blood values in a biracial southern community according to age, sex, and race variations will help in understanding the normative developmental changes in early life and provides background information. Methods. Complete blood counts were obtained from 3,018 free-living children ages 5-17 years from a well-defined black-white community as part of a cardiovascular risk factor screening. Results. For children ages 5-17 years, hemoglobin levels, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and red blood count increased ( P < 0.01) with age. Levels of platelet count and white blood count decreased ( P < 0.0005) with age. Compared with females, males between ages 12 and 17 years have ( P < 0.05) 0.4 × 10 12/liter higher red blood count. 1 g/dl higher hemoglobin, 2% higher hematocrit, 0.2 g/dl higher mean corpuscular hemoglobin concentration, 0.5 × 10 9/liter lower white blood count. 1.4 fl lower mean corpuscular volume, 0.3 pg lower mean corpuscular hemoglobin, and 14 × 1O 9/liter lower platelet count. Compared with blacks, whites have ( P < 0.05) 0.5 10 9/liter higher white blood count, 0.05 10 12/liter higher red blood count, 0.7 g/dl higher hemoglobin, 1.7% higher hematocrit, 2.4 fl higher mean corpuscular volume, 1 pg higher mean corpuscular hemoglobin, and 0.5 g/dl higher mean corpuscular hemoglobin concentration. A positive association was noted among blood count variables and hemoglobin with blood pressure similar to that in adults. Conclusion. Blood values differ by age, sex, and race. These differences change at maturation and should be considered when defining normal and "abnormal" blood values.

Effect of immune-mediated erythrocyte agglutination on analysis of canine blood using a multichannel blood cell counting system.

Blood from six dogs with in vitro immune-mediated erythrocyte agglutination resulted in analytical errors in directly measured counting and sizing functions on a multichannel blood analysis system with histogram capability. Errors in the directly measured values, mean cell volume (MCV), and erythrocyte count were attributed to agglutinated erythrocyte particles that persisted during the relatively short reagent contact time of the analysis. Agglutinated particles less than 240 fl were visible on erythrocyte histograms and resulted in a false low erythrocyte count and false high MCV. Agglutinated cell particles greater than 240 fl were not present on the histogram scale. Because these latter particles exceeded the upper threshold, they did not influence determination of MCV, but resulted in a further decrease in the erythrocyte count. As a result, the other dependent erythrocyte indices were in error. These included false low hematocrit and false high mean corpuscular hemoglobin concentration (MCHC), when compared to corrected reference blood values. Similar errors occurred when analyzing blood samples that were agglutinated in vitro by incubating erythrocytes with incompatible plasma. The counting and sizing errors observed with electronic counting techniques were eliminated or greatly reduced by incubating blood in cell counting diluent for 10 minutes followed by analysis on a single channel counter with attached particle size analyzer. Error in erythrocyte measurement on a multichannel system may be anticipated if there is overt erythrocyte agglutination in a blood sample, an abnormally high MCHC is reported by the system, or subpopulations of large volume (agglutinated cells) are observed on a volume distribution histogram.

Reference ranges and the influence of age and sex on hematologic and serum biochemical values in donkeys (Equus asinus)

SUMMARY Hematologic and serum biochemical values were determined in blood samples from 217 donkeys (Equus asinus). Donkeys were classified on the basis of size, sex, age, and whether they were domestic or feral. Parametric (mean ± 2 sd) and nonparametric (2.5th to 97.5th percentile) reference ranges were calculated for each analyte. For all donkeys, 26 of 46 analytes significantly departed from gaussian distribution. Serum lactate dehydrogenase activity in miniature donkeys was higher than that in other donkeys. Differential leukocyte counts in feral donkeys differed from those in other types in ways that suggested that the former had smaller parasite loads or experienced greater stress. Erythrocyte, lymphocyte, and platelet counts and fibrinogen, glucose, inorganic phosphorus, and potassium concentrations decreased with age. Eosinophil counts, mean corpuscular volume, and plasma protein, serum protein, and serum globulin concentrations increased with age. Female donkeys had significantly (P &lt; 0.05) higher mean corpuscular hemoglobin concentration and leukocyte and neutrophil counts than did male donkeys. Mean corpuscular hemoglobin increased with age, and females had higher values than did males of all age groups. An interaction between age and sex was observed for alkaline phosphatase activity, with a trend for decreased activity with age.

Serum and urine biochemical indicators of nutritional status in adult female collared peccaries, Tayassu tajacu (tayassuidae)

1. 1. Physiological responses of 13 adult female collared peccaries ( Tayassu tajacu) to high quality and low quality diets, fed for 15 weeks, were examined. The low quality diet simulated energy and protein intake of peccaries during poor range conditions resulting from drought. Blood samples were collected after 10 and 15 weeks of dietary treatment; urine samples were collected after 15 weeks of treatment. 2. 2. Females receiving the low quality diet for 15 weeks lost 27.4% of their original body weight, compared to no weight change among high quality-fed females. 3. 3. Red blood cell counts, hematocrits, and hemoglobin concentrations were significantly greater among females fed a high quality diet compared to those receiving a low quality diet. High quality-fed females also had a higher mean corpuscular hemoglobin concentration. Plasma fibrinogen concentration was nearly twice as great among females receiving the low quality diet compared to the high quality group. 4. 4. Consumption of the low quality diet resulted in significantly elevated serum levels of nonesterified fatty acids, alkaline phosphatase, phosphorus, alpha-2 globulin and alpha globulin: beta globulin ratio. 5. 5. Consumption of the low quality diet resulted in significantly lowered serum levels of urea nitrogen, calcium, zinc, calcium: phosphorus, urea index, beta-1 flobulin, beta globulin: albumin ratio, thyroxine and triiodothyronine. 6. 6. Serum levels ofcreatinine, total bilirubin, glucose, cholesterol, gamma glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, potassium, copper, magnesium, sodium chloride, total protein and gamma globulin were unaffected by diet quality. 7. 7. Urine chemistry results suggested pH, osmolarity, albumin, creatinine phosphokinase, calcium and phosphorus concentrations might be useful indices for assessing nutritional status in female peccaries.

Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes.

The concurrence of sickle cell anemia and alpha-thalassemia results in less severe hemolytic anemia apparently as a result of reduced intraerythrocytic concentration of hemoglobin S and its retarded polymerization. We have evaluated the effect of alpha-globin gene number on several interrelated properties of sickle erythrocytes (RBC) that are expected to correlate with the hemolytic and rheologic consequences of sickle cell disease. The irreversibly sickled cell number, proportion of very dense sickle RBC, and diminished deformability of sickle RBC each varied directly with alpha-globin gene number. Sickle RBC density was a direct function of the mean corpuscular hemoglobin concentration (MCHC). Even in nonsickle RBC, alpha-globin gene number varied directly with RBC density. Despite differences in alpha-globin gene number, sickle RBC of the same density had the same degree of deformability and dehydration. These data indicate that the fundamental effect of alpha-thalassemia is to inhibit the generation of sickle RBC having high density and MCHC, and that the other beneficial effects of sickle RBC are secondary to this process. The less consistent effect on overall clinical severity reported for subjects with this concurrence may reflect an undefined detrimental effect of alpha-thalassemia, possibly on the whole blood viscosity or on sickle RBC membrane-mediated adherence phenomena.

Toxicological studies on 5-methoxymethyl-2′-deoxyuridine, a new antiviral agent

Toxic effects of 5-methoxymethyl-2′-deoxyuridine (MMUdR) were studied in White Swiss mice. Pathological, hematological, and clinical chemistry parameters were examined. No morbidity or mortality was observed after administration of MMUdR in a single dosage of 4000 mg/kg and in repeated dosages of 1000 mg/kg daily for 15 days. No gross or histopathological lesions related to MMUdR treatment were observed in the tissues examined from mice of the acute toxicity studies. Histopathological lesions were found in liver and intestine of mice treated with 1000 mg/kg/day for 15 days. These lesions consisted of cytoplasmic vacuolation of hepatocytes and atrophy of intestinal villi. The latter was associated with dilation of the intestine. Control livers contained significantly more mitotic figures than did those of treated animals. The mean corpuscular volume (MCV) of treated mice (4000 mg/kg) was significantly lower than that of controls. After repeated low doses, treated animals exhibited a hemoconcentration effect as evidenced by a lower packed cell volume and MCV and a higher mean corpuscular hemoglobin concentration and total solids in serum. Microscopic examination of marrow smears from control and treated animals from both acute and subacute toxicological studies demonstrated normal hematopoiesis. Differences in serum alkaline phosphatase and serum glutamic oxaloacetic transaminase activities between treated and control mice were observed in the subacute toxicity study. No toxic effect upon fetuses and no teratogenic effects were observed in 152 offspring from mice receiving 500 mg/kg/day of MMUdR for 19 or 21 days.

Erythrocyte Hb-S concentration. An important factor in the low oxygen affinity of blood in sickle cell anemia.

The blood in sickle cell anemia has a very low oxygen affinity and, although 2,3-diphosphoglycerate (2,3-DPG) is increased, there is doubt as to whether this is the only factor responsible. In this study of 15 patients with sickle cell anemia (Hb SS) no correlation was found between oxygen affinity (P(50) at pH 7.13) and 2,3-DPG in fresh venous blood. Whole populations of Hb SS erythrocytes were therefore separated, by an ultracentrifuge technique, into fractions of varying density. The packed red cell column was divided into three fractions; a bottom fraction rich in deformed cells or irreversibly sickled cells (ISC), with a very high mean corpuscular hemoglobin concentration (MCHC); a middle fraction containing cells with the highest content of fetal hemoglobin; and a top fraction containing reticulocytes and discoid cells but free of deformed cells. Oxygen affinity was shifted to the right in all layers (mean P(50) (pH 7.13)+/-1SD: top 46.3+/-2.9 mm Hg: middle 49.8+/-4.9 mm Hg; bottom 61.0+/-5.8 mm Hg) compared with normal blood (top 32.1+/-0.7 mm Hg: bottom 30.1+/-0.5 mm Hg). 2.3-DPG was increased in the top fraction, but was low or normal in the bottom fraction (top 21.8+/-3.4 mumol/g Hb: middle 17.7+/-2.2 mumol/g Hb; bottom 13.8+/-3.1 mumol/g Hb; normal whole blood 14.3+/-1.2 mumol/g Hb). The level of 2,3-DPG in top fractions could not account for the degree of right shift of P(50), and in the middle and bottom fractions the even greater right shifts were associated with lower levels of 2,3-DPG. Top fraction cells depleted of 2,3-DPG had a higher, but still abnormally low, oxygen affinity. A strong relationship was found between oxygen affinity and MCHC. The fractions with the greatest right shift in P(50) had the highest MCHC (top 32.4+/-2.0; middle 36.2+/-3.1; bottom 44.6+/-3.2 g/100 ml, respectively) and the plot of P(50) vs. MCHC showed a positive correlation (r = 0.90, P < 0.001). The red cell population in sickle cell anemia is not homogeneous but contains cells of widely varying Hb F content, 2,3-DPG, and hemoglobin concentration. Paradoxically, the cells with the lowest O(2) affinity have the lowest 2,3-DPG, but they also have the highest concentration of Hb S. The dense, deformed cell called the ISC is but the end stage in a process of membrane loss and consequent increase in hemoglobin concentration. The P(50) of Hb SS blood is, to a large extent, determined by the presence of these cells (r = 0.85, P < 0.001). Increased concentration of Hb S in the cell favors deoxygenation and crystallization even at relatively high P(o2). Lowered affinity for oxygen appears to be closely associated with Hb S concentration and not with 2,3-DPG content.