Increase In Mean Corpuscular Volume Research Articles

Impact of Camel's Milk on Aluminum Chloride (Alcl3) - Induced Toxicity in Rats

The present study was carried out to evaluate the efficiency of camel's milk to ameliorate the toxicity of aluminum chloride AlCl3 on some hematological parameters; hepatic,renal functions andlipids profile; as well ashistopathological alterations of some organs. Forty rats (8 / group) were divided into 5 treatment groups:Group1: Normal rats (negative control); Group2: AlCl3induced toxicity rats (positive control); Group3: AlCl3induced toxicity rats fed with raw camel milk; Group4: AlCl3 induced toxicity rats fed with heat treated camel milk; andGroup5: AlCl3 induced toxicity rats fed with sweet acidophilus camel milk.Rats were treatedby 5ml camel’s milk 10 min before the administration of 1 ml AlCl3 (0.5 mg / kgbody weight); and had their respective doses daily for 30 successive days orally. AlCl3 oral administration resulted in a significant decrease in red blood cells count (RBC's), significant increase in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH); while hemoglobin (Hb), hematocrite (Hct), platelets(plt), reticulocytes (Ret), mean corpuscular hemoglobin concentration (MCHC) did not revealed significant changes; the obtained anemia was macrocytic normochromic. The lipids profile; hepatic and renal functions showed non significant changes between different groups; however, histopathological examination showed variable alterations of varying severity in some organs; besides their response to camel's milk administration. Camel’s milk administration in groups 3, 4, 5 alleviated the toxic effect of AlCl3 with variable degrees between different groups.

Comparison of Therapeutic Efficacy of Ferrous Ascorbate and Iron Polymaltose Complex in Iron Deficiency Anemia in Children: A Randomized Controlled Trial.

To compare the therapeutic efficacy of Ferrous ascorbate (FA) and Iron polymaltose complex (IPC) in Iron deficiency anemia (IDA) in children. A randomized controlled trial (RCT) was conducted at a tertiary care hospital with 125 (1-12 y) children having clinical symptoms and signs of IDA. Participants were randomized into FA group and IPC group. Both the groups received iron salts (FA or IPC) randomly in a dose of 6mg/kg elemental iron for 3 mo and followed up on day 3, day 7, at the end of 1 mo and 3 mo for Hemoglobin (Hb), Mean corpuscular volume (MCV), Red cell distribution width (RDW) and reticulocyte count. Both groups had an improvement in hematological parameters at 3 mo of intervention. The difference in the rise of Hb (g%) at the end of 1 mo in FA group (3.13 ± 1.01) vs. IPC group (2.0 ± 0.85); p = 0.017 and at 3 mo in FA group (4.88 ± 1.28) vs. IPC group (3.33 ± 1.33); p = 0.001 was statistically significant. The difference in the rise of mean Hb was significantly better in FA than the IPC group F [3392] =1.79; p = 0.00 (ANOVA). The difference in the mean increase in MCV (fL) at day 7 in FA group (6.71 ± 8.32) vs. IPC group (2.91 ± 6.16); p = 0.011 and at 1 mo FA group (9.80 ± 8.56) vs. IPC group (5.35 ± 6.11); p = 0.004 was statistically significant. The mean decrease in RDW (%) at 1 mo in FA group (4.23 ± 3.27) vs. IPC group (2.67 ± 1.95); p = 0.005 and at 3 mo in FA group (5.74 ± 3.63) vs. IPC group (4.04 ± 2.17); p = 0.006 was statistically significant. The difference in the rise in mean reticulocyte count at day 3 in FA group (0.88 ± 0.50) vs. IPC group (0.43 ± 1.20); p = 0.017 and at day 7 in FA group (4.00 ± 1.69) vs. IPC group (2.19 ± 1.24); p = 0.001 was statistically significant. F [2294] = 29.2, p = 0.00 (ANOVA). During the study period, the FA group had minor adverse reactions whereas the IPC group had none. Both the iron salts (FA and IPC) used in the treatment of IDA showed statistically significant improvement in the hematological parameters during the 3 mo of intervention. The improvement in hematological parameters was better in FA supplemented patients as compared to IPC.

Variability of red blood cell size predicts all-cause mortality, but not progression to dialysis, in patients with chronic kidney disease: A 13-year pre-ESRD registry-based cohort

BackgroundPrognostic role of red blood cell distribution width (RDW) in patients with chronic kidney disease (CKD) is unclear. Little evidence provides a comprehensive predictive analysis considering both baseline values and longitudinal trajectories of RDW along with mean corpuscular volume (MCV). MethodsWe conducted a comprehensive risk assessment of RDW and MCV in a registry-based cohort of 4621 patients with CKD (age, 20–90 y) receiving multidisciplinary care during 2003 to 2015. Both baseline and longitudinal trajectories of RDW and MCV were modeled as predictors for end-stage renal disease (ESRD) and mortality by using multiple Cox proportional hazards regression models, incorporating time-varying covariates and adjustments for imperative confounding variables. ResultsFully adjusted hazard ratio (HR; 95% CI) of progression to ESRD for each unit increase in RDW and MCV at baseline was 0.97 (0.93–1.02) and 1.00 (0.99–1.01), respectively. Longitudinally, neither RDW nor MCV trajectory was associated with progression to ESRD. For all-cause mortality, fully adjusted HRs (95%CI) were 1.09 (1.04–1.14) for each percent increase in RDW with a linear dose–response relationship and 1.95 (1.47–2.59) for a stable-high RDW trajectory compared with normal RDW trajectory. The effects of RDW on mortality were further augmented in patients with concomitantly high MCV status. Incorporating point-of-care RDW significantly improves the discrimination performance quantified using Harrell C statistics into the existing CKD mortality predictive equation (from 0.770 to 0.784, P = .018). ConclusionsWe support the clinical utility of RDW in predicting all-cause mortality among patients with CKD. The mechanism underlying our findings is critical for CKD risk assessment and management, particularly from malnutrition, inflammation, and atherosclerosis perspectives.

A Direct Correlation between Red Blood Cell Indices and Cognitive Impairment After Aneurysmal Subarachnoid Hemorrhage (aSAH).

Cognitive impairment can occur after aneurysmal subarachnoid hemorrhage (aSAH) though it commonly tends to be neglected. Red blood cell (RBC) indices are associated with long-term functional outcomes, while it is unclear whether RBC indices could be a potential predictor of cognitive decline after aSAH. We aimed to investigate the association between RBC indices and post-aSAH cognitive impairment at 1 year. Patients with aSAH received neuropsychological test by the Montreal Cognitive Assessment (MoCA) and underwent serum and cerebrospinal fluid (CSF) samples test. To determine the association between RBC indices and cognitive impairment after acute aSAH, we adjusted for demographic and vascular risk factors using multivariate logistic regression analysis. Of the 126 patients included in this study, 33% (42/126) of them were diagnosed with cognitive impairment (MoCA＜26). After adjustment for potential confounders, increased mean corpuscular volume (MCV) (OR: 1.36, 95%CI: 1.19-1.55) and mean corpuscular hemoglobin (MCH) (OR: 1.61, 95%CI: 1.25-2.08), reflecting systemic iron status, are more likely to be associated with cognitive impairment after aSAH. In this aSAH population, our data shows the positive association between MCH and MCV and cognitive impairment at 1 year.

Subacute Toxicity of Nerium oleander Ethanolic Extract in Mice

Nerium oleander (N. oleander) is a well-known poisonous shrub that is frequently grown in gardens and public areas and contains numerous toxic compounds. The major toxic components are the cardiac glycosides oleandrin and neriin. The aim of our study was to evaluate the toxic effects of an ethanolic N. oleander leaf extract on haematological, cardiac, inflammatory, and serum biochemical parameters, as well as histopathological changes in the heart. N. oleander extract was orally administered for 14 and 30 consecutive days at doses of 100 and 200 mg of dried extract/kg of body weight in 0.5 mL of saline. The results showed significant increases in mean corpuscular volume, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumour necrosis factor alpha, C reactive protein, alanine aminotransferase, lactate dehydrogenase, creatine kinase and creatine kinase MB, especially at high doses. Marked pathological changes were perceived in the heart tissue. Thus, it can be concluded that exposure to N. oleander leaf extract adversely affects the heart and liver.

Abstract 610: A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study

Abstract Background: In the Agricultural Health Study, a large prospective cohort of pesticide applicators, high lifetime use of the insecticide permethrin was associated with an increased risk of multiple myeloma. However, the biological mechanisms through which this association occurs remain to be fully understood. Methods: Hematologic perturbations were assessed among 33 permethrin-exposed male pesticide applicators enrolled in the Biomarkers of Exposure and Effect in Agriculture study, a molecular substudy within the Agricultural Health Study. Serial blood samples were collected from each participant coinciding with permethrin use including visits during the offseason, an exposure visit the day after use, and for 27 participants a follow-up visit approximately three weeks after use. Complete blood count with white blood cell differential and lymphocyte subsets were collected at each visit. Linear mixed models were used to assess the relationship between permethrin exposure and hematologic parameters, controlling for potential confounders including season of blood draw, age, body mass index, recent cold/infection, and use of other pesticides. Results: A statistically significant increase in the adjusted mean immature granulocyte count (37%, 95% CI=6%, 76%) was observed the day after permethrin use compared to an offseason visit. Statistically significant (P<0.05) alterations in several red blood cell (RBC) parameters were also observed on the day after permethrin use, including decreased RBC count and hemoglobin and increased mean corpuscular volume and RBC distribution width-SD. Decreases in RBC count and hemoglobin, and increased levels of RBC distribution width-SD persisted approximately three weeks after permethrin use. Conclusions: Altered hematologic parameters could be indicative of disrupted hematopoiesis, providing insights into the potential biologic plausibility of the observed association between permethrin use and multiple myeloma risk among pesticide applicators. Impact/Significance: Given the widespread use of permethrin in both residential and commercial settings, our findings may have public health implications beyond occupationally exposed pesticide applicators. Citation Format: Joe Shearer, Laura Beane Freeman, Danping Liu, Gabriella Andreotti, Jennifer Hamilton, Julie Happel, Charles Lynch, Michael Alavanja, Jonathan Hofmann. A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 610.

PS1523 THE OXYGENSCAN: A COMPREHENSIBLE FUNCTIONAL RED BLOOD CELL TEST TO MONITOR TREATMENT EFFICACY IN PATIENTS WITH SICKLE CELL DISEASE

Background:Sickle cell disease (SCD) has multifactorial and complex pathophysiology leading to vaso‐occlusive crises, inflammation, chronic hemolytic anemia and extensive organ damage, resulting in increased morbidity and mortality. To date, there are no laboratory parameters or assays available that can predict disease severity or directly monitor treatment effects.Aims:To validate the oxygenscan, a new method to quantify sickling behavior, as a functional assay to monitor patients with SCD treated with hydroxyurea (HU).Methods:This is an observational multicenter study in children and adults with SCD who started HU treatment. Blood samples were obtained at baseline, and after 1, 3 and 6 months for complete blood count, hemoglobin electrophoresis and oxygenscans on the Laser Optical Rotational Red Cell Analyzer (Lorrca, Zwaag, The Netherlands). The oxygenscan measures red blood cell deformability (expressed as Elongation Index – EI) as a function of oxygen tension (Rab et al, AJH 2019 in press). Key read out parameters are: EImax: maximum elongation during deoxygenation, EImin: minimum elongation after deoxygenation, Point of Sickling (PoS): pO2 (mmHg) at which >5% decrease of EImax during deoxygenation is observed, Slope: slope of the linear part of the deoxygenation curve (Figure 1A).Results:Thirteen patients starting on HU were enrolled. Of these, four patients were followed up to 6 months and seven patients up to 3 months. At 3 months after starting HU treatment all four key oxygenscan parameters were significantly different compared to baseline (all p < 0.05, Figure 1B and C) which stabilized and were comparable to curves measured after 6 months.Levels of fetal hemoglobin (HbF) correlate best with EImin (r = 0.759, p < 0.0001, low values indicate poor deformability under deoxygenated conditions). High absolute reticulocyte counts (ARC) showed a clinically unfavorable increase of oxygen concentration at which RBCs start to sickle (termed PoS), than with lower ARC (Figure 1D). The Slope showed a weak inverse correlation with mean corpuscular hemoglobin concentration (MCHC, r = −0.406, p = 0.016), indicating that increased cellular density accounts for a lower Slope, which increases upon HU treatment. EImin was also associated with mean corpuscular volume (MCV) with a weak correlation (r = 0.451, p = 0.006), which indicates that with an increase of MCV also EImin increases. Our results indicate that oxygenscan parameters including EImin and PoS correlate with established laboratory parameters used in clinical practice to determine treatment efficacy. Although correlations with PoS and Slope were less strong, we observed a significant change upon HU treatment. This suggests involvement of other crucial factors influencing sickling such as intracellular 2,3‐diphosphoglycerate (2,3‐DPG) levels and pH. Based on the results of individual oxygenscans, treatment decisions were made in at least two patients, who showed a clear worsening of the oxygenscan during the 6 months visit. This prompted the physician to review compliance and increase the dosage of HU. These findings show that the oxygenscan can provide additional information and can fill the clinical need for a reliable functional assay in SCD.Summary/Conclusion:The oxygenscan is a versatile and efficient method to monitor HU treatment efficacy in patients with SCD. It is a functional assay that simultaneously determines various RBC features that contribute to individual sickling tendency of patients. It is of added value in personalized treatment of patients with SCD, in particular in titration of HU in children.image

In Utero Exposure to Nicotine Causes Post‐natal Anemia

Almost ¼ of the world population suffers from anemia, a condition characterized by an insufficient number of red blood cells or oxygen‐carrying capacity within the blood. Anemia is associated with fatigue, weakness, and dizziness, and when it occurs early in life it may alter the course of behavioral and cognitive development in human and murine populations causing decreased physical activity and responsiveness. Pregnant women and children are particularly vulnerable to anemia as are individuals who use nicotine. Despite the link between adverse birth outcomes of pre‐ and perinatal nicotine exposure, 11% of US women continue smoking or using alternative nicotine products throughout pregnancy. We hypothesize that in utero exposure to nicotine will result in post‐natal anemia precipitating a characteristic abnormal bone phenotype. To test this hypothesis, wild type C57BL6 males and females were utilized to produce in utero nicotine exposed litters. Drinking water for pregnant dams was supplemented with nicotine. Pups were grown to 15 days postnatal then sacrificed. Blood and whole skulls were collected for complete blood count, micro‐computed tomography (μCT), and histological analyses. Complete blood count data comparing nicotine exposed pups to unexposed controls indicated increased mean corpuscular volume indicative of macrocytic anemia in nicotine exposed mice. Additionally, nicotine exposed pups presented with low platelet counts also associated with anemia. μCT analysis of bone surface compared to bone volume indicated a greater ratio in individuals exposed to nicotine, which suggests weaker pitted bone also associated with anemia. Histological investigation of osteoclast activity indicated greater osteoclast activity in individuals exposed to nicotine. Together, these data indicate that exposure to nicotine in utero precipitates a negative bone phenotype associated with nutritional deficiency and anemia.Support or Funding InformationThis research was supported by the National Institutes of Health (NIH) National Institute of Dental and Craniofacial Research (NIDCR) [R03DE026192, 5T32DE017551 F31DE026684], National Center for Advancing Translational Sciences [UL1TR000062], and Plastic Surgery Foundation [Pilot Award 512114]. This study utilized the facilities and resources of the Medical University of South Carolina Center for Oral Health Research supported by the NIH/NIGM [P30GM103331].This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Analysis of macrocytosis in a tertiary care hospital of North India

Analysis of macrocytosis in a tertiary care hospital of North India - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/2394-6792.2019.0004, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

The impact of hair coat color on physiological variables, reproductive performance and milk yield of Holstein cows in a hot environment

Vulnerable animals to heat stress have been described as ones with dark or black hides due to increasing absorption of solar radiation. The effect of coat color in pluriparous contemporary Holstein cows in a hot environment (mean annual temperature 24.6 °C), on body surface temperature (infrared thermography), physiological and hematological variables as well as milk yield and reproductive performance was assessed using 178 Holstein pluriparous cows (74 predominantly white and 104 predominantly black). Data were collected in the morning and afternoon in July (mean temperature-humidity index 82 units). Body condition score at mid-lactation (128 ± 32 days in milk at the start of the experiment) was higher (P < 0.01) in predominantly white than in black cows (3.3 vs. 3.2). Respiration rate did not differ between groups (72 ± 23 vs. 73 ± 20 breaths/min for white and black cows, respectively, sampling time combined). In contrast, rectal temperature of black cows was 0.1 °C higher (P ≤ 0.01) than white cows, regardless of sampling time. The only significant hematologic change was a slight increase in mean corpuscular volume in black cows (54.7 fL, P < 0.01) compared to white cows (53.8 fL), but it remained within the reference range. Differences due to coat color did not alter body surface temperatures at any time of the day. Conception rates, services per conception, calving intervals and fetal losses were not associated with hair coat color, but cows with predominantly white coat produced 394 kg more (P < 0.01) fat-corrected milk in 305 days compared to cows with predominantly black coat. It was concluded that in this hot-arid environment with cows housed in facilities with extensive cooling, black hair coat moderately reduces 305-d milk yield without affecting milk composition, body surface temperature, and reproductive performance.

Depression, Hematologic Parameters, and Blood Levels of Vitamin B12 in Patients With Laryngopharyngeal Reflux Under Use of Proton Pump Inhibitors.

Objective:The objective of this study was to evaluate and correlate hematologic indices, vitamin B12 levels, and depression in patients with suspected laryngopharyngeal reflux (LPR) treated with proton pump inhibitor (PPI).Methods:This was a prospective study with a population (n = 23) consisted of patients with suspected LPR and treated with 2 daily doses of Omeprazole 40 mg (80 mg or full dose). The study volunteers performed a complete blood count and vitamin B12 dosage before and after 3 and 6 months of treatment, as well as depression screening using the Center of Epidemiologic Studies-Depression (CES-D) questionnaire before and after 6 months of treatment. Scores greater than 16 were considered as suggestive of depression.Results:The mean score on the CES-D scale of study participants at baseline significantly decreased after 6 months of treatment. A significant decrease was observed in the red blood cells count (RBC) after 6 months in relation to 3 months. Significant increases in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were observed from 3 months to 6 months in this study. Vitamin B12 levels increased significantly between baseline and after 6 months of treatment.Conclusion:Decreased scores on the CES-D scale were associated with increased MCV values, with no association with vitamin B12 levels. However, vitamin B12 levels also increased significantly after 6 months of treatment with PPI.

Impact on the hematopoietic system by alcoholism and the influence of duration of consumption

Background: The abuse of alcohol brings with it untold misery in the form of health-related problems as well as social issues. Chronic misuse of alcohol affects literally every aspect of bodily functions and organ systems functioning. Aims and Objectives: This study’s aim was to observe the effect of alcoholism on select blood parameters. Materials and Methods: A total of 50 subjects who met the criteria for alcoholism and other prescribed inclusion criteria, and 50 age- and sex-matched controls formed the study population. Random blood samples obtained from patients as well as controls were used to estimate complete blood count (hemoglobin [Hb], red blood corpuscle (RBC) count, total leukocyte count (TLC), packed cell volume (PCV), mean corpuscular volume (MCV), and platelet count). Duration of alcohol consumption was also noted. Correlational analysis and t-test were the statistical tests adopted. Results: There were significantly reduced values for Hb, RBC count, PCV, and platelet count in alcoholics, and a significant increase in MCV in the same group compared to controls. TLC numbers were similar in both groups, and except for PCV, no other parameters showed any significant correlation with the duration of alcohol consumption. Conclusion: Excessive alcohol consumption affects the erythrocytes and thrombocytes while showing no effect on the leukocytes. In general, duration of alcohol consumption does not seem to influence the severity of these changes.

Neurological symptoms of vitamin B12 deficiency: analysis of pediatric patients.

SUMMARYVitamin B12 is one of the essential vitamins that affect various systems in the body, including the central nervous system. Vitamin B12 plays an important part in the metabolism of the nervous system, although its exact role under pathological conditions is not fully understood. The purpose of this study was to emphasize the importance of early diagnosis of vitamin B12 deficiency in the light of the characteristics of the patients enrolled. This retrospective, clinical study included 38 children with neurological symptoms of vitamin B12 deficiency. Records of 38 patients referred to a single center of the university hospital outpatient child neurology clinic due to neurological symptoms of vitamin B12 deficiency between February 2012 and December 2013 were evaluated retrospectively. Patients aged 0-18 years with symptoms including syncope, dizziness, convulsion, hypotonia, developmental retardation, tremor, ataxia, tingling sensations and paresthesia, blurring of vision, fatigue and concentration difficulty caused by vitamin B12 deficiency were included in the study. Patient neurological findings included syncope (n=6), dizziness (n=4), hypotonia (n=9), inability to sit or walk without support, or gait ataxia (n=2), convulsion (n=4), hand tremor (n=1), tingling sensations and paresthesia (n=3), vision blurring (n=1), fatigue and concentration difficulty (n=8). All patients with neurological symptoms of vitamin B12 deficiency recovered within one month after vitamin B12 supplementation. In conclusion, clinical characteristics of vitamin B12 deficiency are broad and nonspecific and may not be associated with anemia and increased mean corpuscular volume. Since different clinical characteristics can be seen without anemia, awareness and cautious approach are essential in order to avoid severe clinical disease, especially in children from underdeveloped countries.

TOXICIDADE DO ÓLEO ESSENCIAL DE Lippia origanoides EM TAMBAQUI (Colossoma macropomum) E SEU EFEITO FRENTE í­â‚¬ Aeromonas hydrophila

O presente estudo avaliou a toxicidade do óleo essencial de Lippia origanoides em tambaqui (Colossoma macropomum) e sua atividade in vivo frente í­Â Aeromonas hydrophila. Para os testes de toxicidade, tambaquis foram expostos a 0, 5, 10, 12,5, 15, 17,5 e 20 mg L-1 do óleo essencial de L. origanoides por 96 horas. A concentração média letal (CL50) foi estimada em 15,2 mg L-1. Após exposição dos tambaquis í­Â s concentrações subletais de L. origanoides (7,6 e 11,4 mg L-1) por 96 horas, poucas alterações hematológicas e bioquí­­micas como aumento no volume corpuscular médio e decréscimo nos valores de proteí­­nas totais foram observadas na concentração de 7,6 mg L-1, o que não compromete a homeostase orgí­¢nica dos peixes. Tambaquis experimentalmente infectados com A. hydrophila alcançaram maior taxa de sobrevivência (79,2%) após banho terapêutico com 10 mg L-1 do óleo essencial de L. origanoides. Portanto, o tambaqui exibe moderada tolerí­¢ncia ao óleo essencial de L. origanoides e este óleo tem potencial para uso no tratamento de tambaqui (C. macropomum) infectado com A. hydrophila.

Consistent Compliance with Hydroxyurea and Hematology Measures during L-Glutamine Therapy for Sickle Cell Anemia

Background. Oxidative stress contributes to the pathophysiology of sickle cell anemia (SCA). Oral l-glutamine increases the proportion of reduced NAD in sickle erythrocytes,1 which may decrease oxidative stress and SCA complications.2 Recently, a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial of l-glutamine in SCA reported that the l-glutamine group had fewer pain crises and hospitalizations over 48 weeks of treatment than the placebo arm.3 There was a consistent treatment effect of l-glutamine in subjects who used and did not use hydroxyurea. The purpose of the present analysis was to determine if there was consistent use of hydroxyurea in both arms of the trial and if l-glutamine therapy led to a reduction in hemolysis and an amelioration of anemia.Methods. Because increase in mean corpuscular volume (MCV) is a sensitive indicator of hydroxyurea therapy,4 we used MCV as a surrogate marker of hydroxyurea compliance. We analyzed MCV at 4-week intervals according to hydroxyurea therapy separately in the l-glutamine and placebo arms. We also analyzed hemoglobin concentration and reticulocyte count at 12-week intervals according to experimental treatment with l-glutamine versus placebo as stratified by hydroxyurea use. We imputed missing variables by carrying the last measured value forward. We used the student t-test to compare linear variables, Pearson chi square to compare categorical variables and repeated measures analysis of variance to analyze trends over time.Results. The patients receiving l-glutamine and placebo were well matched (Table 1). During the 48-week trial, the MCV was consistently greater in patients using hydroxyurea than those not using hydroxyurea in both the l-glutamine arm (Figure 1) and the placebo arm (Figure 2). Furthermore, there was no significant change over 48 weeks in the MCV in the patients using hydroxyurea in either arm (P >0.7). In the hydroxyurea group, there were no significant differences according to experimental therapy with l-glutamine versus placebo in hemoglobin concentration or reticulocyte count at 12 weekly intervals. In the group not using hydroxyurea, the hemoglobin concentration was significantly higher at baseline in patients given l-glutamine compared to those given placebo, but this observation did not persist at the subsequent determinations; reticulocyte counts did not differ at any time point (Table 2). We performed many multivariate and repeated measures analyses of hemoglobin concentration and reticulocyte count that adjusted for age, gender and blood transfusions, but did not observe evidence that l-glutamine therapy was associated with an increase in hemoglobin concentration and/or a decline in reticulocyte count.Discussion. Based on the MCV, patients who were assigned to hydroxurea complied with hydroxyurea therapy at baseline and throughout the study; this supports the concept that the beneficial clinical effects of l-glutamine therapy for SCA are additive to those of hydroxyurea. Therapy with l-glutamine did not reduce hemolysis or improve anemia, which parallels observations with therapy with an antibody against the adhesion molecule, P-selectin.5 The mechanism whereby l-glutamine leads to reduced vaso-occlusive complications in SCA requires further investigation. Glutamine levels are lower in sickle erythrocytes compared to erythrocytes from healthy volunteers.6 L-Glutamine reduces intercellular adhesion molecule expression in endothelial cells,7 decreases adhesion of sickle erythrocytes to endothelial cells,8 attenuates the expression of endothelial adhesion molecules and T cell migration markers when the intestines are injured, 9,10 and inhibits IL-6 and TNF-α production in LPS-stimuated monocytes.11 Future research will need to assess the effect of l-glutamine on redox potential, adhesion molecule expression, and inflammatory marker expression in erythrocytes, other circulating blood cells and the vascular endothelium.ReferencesAm J Hematol. 1998;58(2):117-121.IUBMB Life. 2012;64(1):72-80.N Engl J Med. 2018;379(3):226-235.Medicine (Baltimore). 1996;75(6):300-326.N Engl J Med. 2017;376(5):429-439.Blood. 2008;111(1):402-410.J Reprod Med. 2006;51(3):193-198.BMC Blood Disord. 2005;5:4.Eur J Pharmacol. 2010;643(2-3):304-315.Mediators Inflamm. 2014;2014:837107.Cytokine. 2013;62(1):52-57. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Gradient Relationship between Increased Mean Corpuscular Volume and Mortality Associated with Cerebral Ischemic Stroke and Ischemic Heart Disease: A Longitudinal Study on 66,294 Taiwanese

The gradient relationship between mean corpuscular volume (MCV) and mortality due to ischemic vascular disease has not been researched using a large-scale population-based study. This study evaluated the association between MCV and death attributable to cerebrovascular disease (CVD) and cardiovascular disease (CAD) in a large population- and community-based Taiwanese cohort. A longitudinal study with a 9-year follow-up was conducted to evaluate individuals aged 20 years or older who had participated in the Keelung (the northernmost city in Taiwan) community-based integrated screening (abbreviated as KCIS) program since September 1999. The mortality rates associated with CVD and CAD were classified across a range of different MCV levels. Increased MCV levels were associated with an increased risk of CVD/CAD-related death (adjusted hazard ratio [aHR] = 1.42, trend test P = 0.0119). Marginally statistically significant associations were noted for specific deaths from ischemic heart disease (aHR = 1.44, trend test P = 0.0992) and cerebral ischemic stroke (aHR = 1.66, trend test P = 0.0667), respectively, but no significant gradient relationship was noted for death from cerebral hemorrhage stroke (aHR = 1.23, trend test, P = 0.6278). A gradient relationship between baseline MCV level and CVD/CAD-related death was noted, but whether such gradient relationships existed for two specific deaths and how these relationships may be confounded by extraneous factors that were not considered here should be investigated in the future.

EFFECT OF RUTIN AGAINST HIGH-FAT DIET AND ALCOHOL-INDUCED ALTERATIONS IN HEMATOLOGICAL VARIABLES OF RATS

Objectives: Alcohol abuse leads to several diseases and millions of death worldwide. High-fat diet (HFD) is major contributor of non-alcoholic liver diseases and obesity. Combined consumption of HFD and alcohol has deleterious effect on blood cells. This study was carried out to evaluate the protective effect of rutin against combined consumption of HFD and alcohol-induced hematological alterations.Methods: HFD 30% and ethanol 10% were administered for 4 weeks for induction of toxicity. Rutin (10, 20, and 40 mg/kg) and 50 mg/kg dose of silymarin were administered along with HFD and alcohol for 4 weeks.Results: Combined consumption of HFD and alcohol increased mean corpuscular volume, total leukocytes count, eosinophil and monocyte, and decreased hematocrit and platelets. Administration of rutin improved hematological variables altered by HFD and alcohol consumption.Conclusion: The present study concluded that administration of rutin may alleviate HFD and alcohol-induced hematological alterations by scavenging free radicals generation.

Epilepsili Çocuklarda Antiepileptik İlaçların Tam Kan Sayımı Üzerine Etkileri

Objective: Since antiepileptic drug use is long-term, it may be important to know their effects on blood cell counts during the management of these patients. However, these effects have not been adequately evaluated in epileptic children. In our study, the effects of valproate, levetiracetam and carbamazepine on complete blood counts were assessed in children. Material and Methods: Material and methods: Consecutive epilepsy patients under monotherapy were reviewed retrospectively. Eighty patients, whose data were available before the treatment and at 2-6 months and 9-16 months after treatment initiation were included in the study. The ages at the start of the treatment were taken into consideration. Hemoglobin, hematocrit, erythrocyte, platelet and leucocyte counts, leukocyte subset percentages and the mean volume and distribution width of the erythrocytes and thrombocytes were recorded. Results: There were no statistically significant differences between the levels at pre-treatment and at 2-6 and 9-16 months after treatment initiation in the patients treated with levetiracetam (n=25) and carbamazepine (n=20). In the valproate group (n=35), there was an increase in mean corpuscular volume and monocyte percentage, and a decrease in platelet counts, in the first six months (p=0.015, p=0.001, p=0.005, respectively). At 9-16 months, the lymphocyte percentage increased while the neutrophil and eosinophil percentages decreased (p=0.016, p=0.014, p=0.01, respectively) in this group. Conclusion: In our study, valproate caused an increase in the percentage of lympho-monocytes and mean corpuscular volume, and a decrease in the platelet count, neutrophil and eosinophil percentages. These effects seem to be related to the fact that valproate is a histone deacetylase inhibitor.

Hematologic Perturbations among Pesticide Applicators Recently Exposed to Permethrin in the Agricultural Health Study

In the Agricultural Health Study (AHS), a large prospective cohort of pesticide applicators, exposure to the pyrethroid insecticide permethrin is associated with an increased risk of multiple myeloma (MM), a hematologic malignancy with an unfavorable prognosis. To gain insight into the biological mechanisms underlying this association, we assessed potential hematotoxic effects of permethrin, in a longitudinal study of 35 permethrin-exposed male pesticide applicators in the AHS. Serial blood samples were collected from each participant in the off-season, the day after permethrin use, and approximately 3 weeks after use. At each time point, we performed a complete blood count with white blood cell differential and measured lymphocyte subsets. We used linear mixed models to assess the relationship between permethrin exposure and cell counts, controlling for season, age, BMI, recent cold/infection (&amp;#8804;7 days), and use of other pesticides (&amp;#8804;30 days). We observed a statistically significant increase in the geometric mean of immature granulocytes (31%, 95% CI&amp;#61;6%, 63%) on the day after permethrin use relative to off-season levels, but not 3 weeks after use. Statistically significant (P&amp;lt;0.05) alterations in several red blood cell parameters were also observed on the day after permethrin use, including decreased red blood cell count, hemoglobin, and hematocrit and increased mean corpuscular volume and red blood cell distribution width-SD. Red blood cell count, hemoglobin, and hematocrit remained significantly decreased 3 weeks after permethrin use. Increased immature granulocytes are indicative of an inflammatory response and enhanced bone marrow activity, and sustained decreases in red blood cell parameters may be a result of increased oxidative stress. Our results suggest inflammatory and hematologic effects of permethrin exposure, and identify targeted cell populations for future mechanistic studies to elucidate the relationship between permethrin use and MM risk.

Toxicological effects of trichlorfon on hematological and biochemical parameters in Cyprinus carpio L. following thermal stress

Trichlorfon is a moderately toxic organophosphate pesticide that is widely used in aquaculture. This study investigated the effects of trichlorfon on hematological parameters, biochemical factors, and stress reaction in Cyprinus carpio L. The fish were exposed to acute concentrations of trichlorfon (0, 0.5, 1.0, 2.0, and 4.0 mg L−1) at 25 °C and 15 °C for 1 and 2 weeks, after which several parameters were evaluated to assess the effects of the pesticide. Significant decreases were observed in red blood cell (RBC) Count, hemoglobin (Hb) level, hematocrit (Ht), and plasma protein levels after each exposure period. In contrast, notable increases in mean corpuscular volume (MCV), mean cell hemoglobin (MCH), calcium, and glucose levels were observed in the trichlorfon-treated groups. Additionally, there were significant increases in the plasma levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and alkaline phosphatase (ALP) following the exposure to trichlorfon. Furthermore, the results showed a relationship between toxic stress and increment in HSP70 and cytochrome P450 1A (CYP1A) expression over time. Ht, MCV, MCH, and the value of other biochemical parameters were quite lower at 15 °C than their corresponding values were at 25 °C, which indicated the decreased physical activity at 15 °C. The results of the present work indicate that acute exposure to trichlorfon and thermal stimulus could damage erythropoietic tissue. Additionally, hepatocytes function and physiological mechanisms could be impaired. Ht, glucose, GOT, GPT, HSP70, and CYP1A levels might be useful biomarkers of trichlorfon toxicity in contaminated aquatic ecosystems.