Toxicity of High-Dose Chlorambucil in Wistar Rats

The aim of this study was to determine the maximum tolerated dose and the haematological and non-haematological toxicity of chlorambucil in male Wistar rats. Chlorambucil (pulverized pills or pure substance) was dissolved in ethanol and administered orally at a dose ranging from 0.15 to 50 mg/kg/day for 5 days. Evaluations of experimental rats included general clinical state of health, body weight, haematological indicators (red blood cell count, white blood cell count, platelet count, differential leukocyte count, packed cell volume and haemoglobin concentration), biochemical plasma indicators (urea, creatinine, ALP, ALT, AST, Na, K, Cl), immunophenotype of leukocytes (CD3, CD8 and CD4 markers), as well as histopathology. Doses of chlorambucil from 0.15 to 0.75 mg/kg/day had no effect on the general clinical state of health as well as on other laboratory variables. Doses of 2–12 mg/kg/day were well tolerated, but mild myelotoxicity (leukopaenia) and elevated activities of liver transaminases were found. Doses of 20 to 50 mg/kg/day were myelotoxic (p < 0.01) with prevailing lymphopaenia but only minimum effects on red blood cells and platelets. Histology revealed pneumotoxicity, nephrotoxicity and damage to the gastrointestinal tract. Doses of 40 and 50 mg/kg/day resulted in acute lethal effects in 50% and 75% of individuals, respectively. Results of this study are intended for use in the testing of chlorambucil in combination with other drugs as a conditioning for bone marrow transplantation.

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Confounding influences of malnutrition and Plasmodium falciparum and Schistosoma haematobium infections on haematological parameters in school children in Muyuka, Cameroon

BMC Infectious Diseases ◽

10.1186/s12879-021-06201-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Irene Ule Ngole Sumbele ◽

Ofon Vitalis Otia ◽

Lorraine Francis ◽

Orelien Sylvain Mtopi Bopda ◽

Calvin Bisong Ebai ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Blood Cell ◽

Cell Count ◽

Schistosoma Haematobium ◽

Haemoglobin Concentration ◽

Haematological Parameters ◽

Blood Cell Count ◽

Malaria Parasites ◽

Mean Cell Volume ◽

Distribution Width

Abstract Background School-aged children (SAC) are a high-risk demographic group for infectious diseases and malnutrition. The objective of this study was to assess the burden and the effect of Plasmodium falciparum and Schistosoma haematobium infections on the haematological indices in SAC and the confounding influence of malnutrition on the outcomes. Methods This cross-sectional study was conducted in SAC 4–14 years old living in Ikata, Bafia and Mile 14-Likoko in Muyuka, Cameroon. Anthropometric measures of malnutrition were obtained and blood samples collected were used for detection of malaria parasites by Giemsa-stained blood films using light microscopy and complete blood count analysis using an automated haematology analyser. Urine samples collected were used to detect micro haematuria with the aid of reagent strips and the eggs of S. haematobium by urine filtration technique. Multiple linear regression model was used to examine influence of independent variables on haematological parameters. Results Out of the 606 SAC examined, the prevalence of single infections with Plasmodium or S. haematobium and co-infection with both parasites was 16.2, 16.3 and 8.3%, respectively. Overall, malaria parasite (MP), urogenital schistosomiasis, malnutrition, anaemia, haematuria, microcytosis and thrombocytopenia was prevalent in 24.4, 24.6, 25.9, 74.4, 12.2, 45.4 and 11.1% of SAC, respectively. A significant linear decline (P = 0.023) in prevalence of P. falciparum infection with the severity of stunting was observed. Factors that significantly influenced haematological parameters included haemoglobin: age, stunting and MP; haematocrit: age and MP; white blood cell count: age; red blood cell count; age and MP; lymphocyte counts: stunting; mean cell volume: age; mean cell haemoglobin: age and stunting; mean cell haemoglobin concentration: sex, stunting and red cell distribution width-coefficient of variation: sex, age and stunting. Conclusions Malnutrition, Plasmodium and S. haematobium infections are common while anaemia is a severe public health problem in Muyuka, Cameroon. The interaction between haematological parameters with malaria parasites as well as linear growth index was negative and other interactions indicate systemic inflammation. While findings provide contextual intervention targets to ensure the judicious use of the limited resources, there is need for regular monitoring and proper treatment to improve the health of the underserved population.

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Studies on the toxicity of an aqueous extract of the leaves of Abrus precatorius in rats

Onderstepoort Journal of Veterinary Research ◽

10.4102/ojvr.v74i1.137 ◽

2007 ◽

Vol 74 (1) ◽

Cited By ~ 15

Author(s):

A.A. Adedapo ◽

O.A. Omoloye ◽

O.G. Ohore

Keyword(s):

Blood Cell ◽

Cell Count ◽

Aqueous Extract ◽

Haemoglobin Concentration ◽

Total Serum Protein ◽

Total Serum ◽

Blood Cell Count ◽

Abrus Precatorius ◽

White Rats ◽

Histopathological Studies

The toxic effects of an aqueous extract of Abrus precatorius were studied in 20 male white rats over a period of 18 days. The rats were divided into four groups of five rats per group. Those in Group A served as controls while the rats in Groups B, C and D were dosed per os with 400 mg/kg, 800 mg/kg and 1 600 mg/kg of the extract, respectively. Blood samples were collected for haematological and biochemical analysis and specimens of the liver, kidney and testes were taken for histopathological studies. The study showed that the extract of A. precatorius caused decreased levels of packed cell volume, haemoglobin concentration, red blood cell count, white blood cell count, mean corpuscular volume and mean corpuscular haemoglobin. The extract also resulted in increased levels of total serum protein, albumin, alanine amino transaminase, aspartate amino transferase, alkaline phosphatase and total bilirubin. Histologically, testicular degeneration characterized by decreased numbers of lining cells of the epithelium as well as reduction in sperm cells with presence of scattered Sertoli cells were noted. The study thus showed that aqueous extract of Abrus precatorius is toxic and caution should be exercised in its use for medicinal purpose.

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Haematological Profiles of Pigs on Different Farms Reflect Their Health Status

10.21203/rs.3.rs-644732/v1 ◽

2021 ◽

Author(s):

Irena Golinar Oven ◽

Alenka Nemec Svete ◽

Melita Hajdinjak ◽

Jan Plut ◽

Marina Stukelj

Keyword(s):

Health Status ◽

Blood Cell ◽

Cell Count ◽

White Blood Cell ◽

Haemoglobin Concentration ◽

Haematological Parameters ◽

Blood Cell Count ◽

Blood Samples ◽

Corpuscular Haemoglobin ◽

Mean Corpuscular Haemoglobin

Abstract BackgroundHaematological examination is an important diagnostic tool in the assessment of pig health status. The present study aimed to assess haematological parameters in pigs of different age categories from six farrow-to-finish farms differing in herd health status. The following pig categories were included: 5 age groups of growers (5, 7, 9–10, 11 and 12–13 weeks-old), fatteners and breeding pregnant sows. Individual blood samples for determining complete blood count and white blood cell differential count were taken and group samples of oral fluid and faeces were collected from each animal category in each of the six farms and tested for the detection of Porcine Circovirus Type 2 (PCV2), Porcine Reproductive and Respiratory Virus (PRRSV), and Hepatitis E Virus (HEV) using PCR, RT-PCR, and qRT-PCR protocols. Individual blood samples were analysed using an automated laser-based haematology analyser. The following haematological parameters were reported: white blood cell count (WBC), red blood cell count (RBC), haemoglobin concentration (Hb), haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet count (PLT), and percentage and number of neutrophils, lymphocytes, monocytes, eosinophils, basophils, and "large unstained cells" - LUCs. ResultsOn farms free of PRRSV, PCV2 and HEV, age had significant effect on the following parameters: WBC, Hb, MCH, MCHC, PLT, percentage of neutrophils, lymphocytes and eosinophils and absolute numbers of neutrophils, lymphocytes, monocytes, basophils and LUCs. On farms with PRRS, PCV2 and/or HEV, age significantly affected all observed blood parameters except the percentage of LUCs. The percentages of lymphocytes, MCV and Hct were significantly lower by PRRSV while WBC, PLT, percentage and absolute number of neutrophils, basophils and LUCs increased. Significantly lower percentages of lymphocytes and increased percentages and absolute numbers of neutrophils, eosinophils and basophils were caused by PCV2 presence. Significantly lower percentage of lymphocytes and MCV and increased RBC, Hb, percentage and number of basophils and percentage of neutrophils were caused by HEV. Conclusions Alterations of haematological parameters reflected the health status of pigs of different categories on infected and on non-infected farms. Age-related changes in haematological parameters occurred in clinically healthy and in infected pigs.

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Blood Parameters in Natural Populations of Trichosurus Species (Marsupialia: Phalangeridae). I. Age, Sex and Seasonal Variation in T. Caninus and T. Vulpecula. Ii. Influence of Habitat and Population Strategies of T. Caninus and T. Vulpecula.

Australian Journal of Zoology ◽

10.1071/zo9790913 ◽

1979 ◽

Vol 27 (6) ◽

pp. 913 ◽

Cited By ~ 23

Author(s):

JL Barnett ◽

RA How ◽

WF Humphreys

Keyword(s):

Body Weight ◽

Seasonal Variation ◽

Blood Cell ◽

Cell Count ◽

Red Blood Cell ◽

Plasma Glucose ◽

Haemoglobin Concentration ◽

Blood Parameters ◽

Blood Cell Count ◽

Red Blood Cell Count

Age, sex and seasonal related changes in body weight and blood parameters were determined for T caninus and T. vulpecula, whose distribution overlapped in part of the study area. In T. caninus age-related changes occurred in body weight, mean plasma glucose and protein concentrations and haematocrit. Seasonal changes occurred in plasma glucose and protein concentrations, haemoglobin concentration and red blood cell count. There were sexual dimorphisms in haematocrit, haemoglobin concentration and red blood cell count in both species; the mean values were greater in males. T. vulpecula also exhibited a sexual dimorphism in body weight (males > females). The only seasonal change in T. vulpecula was in haemoglobin concentration. Comparison of the species as adults showed that T. caninus had higher mean levels of body weight, haematocrit and haemoglobin concentration, while plasma lipid concentration and red blood cell counts were greater in T vulpecula. These species differences may be a reflection of the diets of the two species. In addition the measured parameters showed greater seasonal variation in T. caninus, a K-selected species, than in T. vulpecula, which is more r-selected.

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Acute Myeloid Leukemia: The Outcome Is Determined By Age, Genetic Group, White Blood Cell Count, Lactate Dehydrogenase, Rather Than By Chemotherapy Intensity

Blood ◽

10.1182/blood.v122.21.1447.1447 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1447-1447

Author(s):

Thomas Buchner ◽

Wolfgang E. Berdel ◽

Utz Krug ◽

Claudia Haferlach ◽

Susanne Schnittger ◽

...

Keyword(s):

Overall Survival ◽

Lactate Dehydrogenase ◽

Blood Cell ◽

Cell Count ◽

White Blood Cell Count ◽

Standard Dose ◽

High Dose ◽

Blood Cell Count ◽

Younger Patients ◽

Baseline Characteristics

Abstract Background Data on benefit and toxicity by treatment intensification for AML are now available and allow rediscussing current dosing. Methods In a multicenter trial involving patients between 16 and 86 years of age, patients below 60 years received uniform double induction by the 1st course with standard dose araC/ daunorubicin (60mg/m²x3)/ thioguanine followed by the 2nd course with high-dose araC (3g/m²x6)/ mitoxantrone (10mg/m²x3), or randomly two high-dose courses. As age adaption patients of 60y or older received the 2nd course only in case of persistent blasts, and high-dose araC at 1 instead of 3g/m². Post remission treatment was consolidation and maintenance or randomly autologous stem cell transplantation in younger patients. Results 3369 patients entered the trial with 1843 patients 60y or older. A multivariate analysis identified age as continuous variable, favorable cytogenetics/ molecular genetics, unfavorable cytogenetics, white blood cell count and lactate dehydrogenase as categorical variables to be risk factors predicting complete remission, overall survival as well as relapse free survival. To separate the age effect from the treatment effect, two subgroups of similar age and baseline characteristics but different treatment were compared. Thus, the 239 patients aged 57-59 and the 336 patients aged 60-62 years shared not only similar age but also similar baseline characteristics, while their treatment by protocol and age adaption differed substantially. The difference as expressed by the cumulative araC dosis amounted to a factor of 3.6, which however did not translate into a different overall survival (equally 28%) or relapse rate (equally 70%) at 5 years. In contrast to different treatment, different age had a strong effect on outcome. Thus, the survival in patients aged 16-46y was 65% at 5 years versus 40% in those of 47-59y receiving the same treatment (p< 0.001). A corresponding age related difference was also found between the patients of 60-66y and those of 67-86y (p< 0.001) receiving the same age adapted treatment. As shown by others in patients of 18-60y doubling an intermediate cumulative dose of araC produced excessive toxicity without therapeutic benefit (Löwenberg B et al. NEJM 2011; 364: 1027-36), while high dose daunorubicin (90mg/m²) instead of standard dose (45mg/m²) improved the remission rate and survival in younger patients (Fernandez H et al. NEJM 2009; 361: 1249-59) and older patients of 60-65y (Löwenberg B et al. NEJM 2009; 361: 1235-48). No comparable data are available about daunorubicin 60mg/m² the standard in present study. Conclusion Age and disease biology rather than chemotherapy intensity are the main determinants of outcome in AML. Once a certain intensity and antileukemic effect has been achieved, a further escalation does not seem to overcome the age factor in AML. Present data require rediscussing current chemotherapy dosing and treatment alternatives. Disclosures: No relevant conflicts of interest to declare.

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Prevalence of Anaplasma ovis and its effects on haematology of apparently healthy Sahel goats in Maiduguri, Nigeria: A Preliminary study

Savannah Veterinary Journal ◽

10.36759/svj.2017.006 ◽

2018 ◽

pp. 53-57

Keyword(s):

Blood Cell ◽

Cell Count ◽

Haemoglobin Concentration ◽

Well Being ◽

Economic Losses ◽

Blood Cell Count ◽

Anaplasma Ovis ◽

Corpuscular Haemoglobin ◽

Mean Corpuscular Haemoglobin ◽

Apparently Healthy

Introduction: Anaplasma ovis is an intraerythrocytic rickettsial pathogen that causes clinical symptoms and huge economic losses in flocks. This study was designed to determine the prevalence and effects of Anaplasma ovis on the haematology of apparently healthy Sahel goats in Maiduguri. Methods: Blood samples were randomly collected from one hundred (100) Sahel goats from both farm and abattoir in the study area. Parasitological and haematological analyses were carried out on the collected samples using a standard technique. Results: Out of 100 goats sampled, seven (7) were positive with an overall prevalence of 7%. The prevalence was higher in the male 5 (5%) than in the female 2 (2%) with no significant association between sexes (p > 0.05). The haematological parameters of infected and uninfected goats were within normal range except for mean corpuscular volume (MCV) of infected goats. The MCV of infected and uninfected goats varied significantly (p < 0.05) while the packed cell volume, haemoglobin concentration, red blood cell count, white blood cell count, mean corpuscular haemoglobin concentration and mean corpuscular haemoglobin of infected and uninfected goats were not significantly (p > 0.05) affected. Significance: Natural infection in apparently healthy goats in Maiduguri was found not to have an obvious effect on the haematology of the infected animals. There is a need for prevention and control programs against this pathogen in the study area. This, when carried out, will improve the production potential of these animals and economic well-being of the owners.

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Soluble CD4, soluble CD8, soluble CD25, lymphopoieitic recovery, and endogenous cytokines after high-dose chemotherapy and blood stem cell transplantation

Blood ◽

10.1182/blood.v84.10.3550.bloodjournal84103550 ◽

1994 ◽

Vol 84 (10) ◽

pp. 3550-3557 ◽

Cited By ~ 1

Author(s):

AD Ho ◽

M Maruyama ◽

A Maghazachi ◽

JR Mason ◽

S Gluck ◽

...

Keyword(s):

Stem Cells ◽

Blood Cell ◽

Cell Count ◽

High Dose Chemotherapy ◽

High Dose ◽

Nk Activity ◽

Blood Cell Count ◽

Gm Csf ◽

Transient Elevation ◽

Soluble Cd4

Mononuclear cell preparations from peripheral blood after mobilization with hematopoietic growth factors have been shown to induce accelerated neutrophil and platelet recovery as compared with that induced by autologous bone marrow transplantation after myeloablative chemotherapy. Because these mononuclear cell products contain many immunocompetent cells other than hematopoietic progenitors, these accessory cells might contribute to the rapid immunohematopoietic reconstitution. We have monitored the concentrations of soluble CD4 (sCD4), sCD8, and sCD25; the recovery of the lymphocyte subsets and of natural killer (NK) cells; and the endogenous levels of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), IL-6, and granulocyte-macrophage-CSF (GM-CSF) in 12 patients who underwent high- dose chemotherapy supported by blood stem cells that were obtained by mobilization with chemotherapy and GM-CSF. The concentrations of both G- CSF and IL-6 peaked at 7 days after reinfusion of stem cells, and this transient elevation preceded the increase in the white blood cell count by approximately 5 to 7 days. The levels of sCD4 and sCD8 increased to a maximum on day 21, and the time to peak levels coincided with the maximum increase in white blood cell count, absolute neutrophil count, or lymphocytes. The levels of sCD25 were found to be elevated from day 7 to day 21. Statistically, the increases in sCD4, sCD8, sCD25, G-CSF, and IL-6 were highly significant, whereas there were no significant changes in IL-3 and GM-CSF. A rapid recovery of the NK activity was found in all 8 of the patients who could be monitored for this assay. Therefore, our study suggests that recovery of CD4+ cells, CD8+ cells, and NK activity coincided with that of neutrophils, which is preceded by a marked, but transient, elevation of IL-6 and G-CSF.

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Soluble CD4, soluble CD8, soluble CD25, lymphopoieitic recovery, and endogenous cytokines after high-dose chemotherapy and blood stem cell transplantation

Blood ◽

10.1182/blood.v84.10.3550.3550 ◽

1994 ◽

Vol 84 (10) ◽

pp. 3550-3557 ◽

Cited By ~ 17

Author(s):

AD Ho ◽

M Maruyama ◽

A Maghazachi ◽

JR Mason ◽

S Gluck ◽

...

Keyword(s):

Stem Cells ◽

Blood Cell ◽

Cell Count ◽

High Dose Chemotherapy ◽

High Dose ◽

Nk Activity ◽

Blood Cell Count ◽

Gm Csf ◽

Transient Elevation ◽

Soluble Cd4

Abstract Mononuclear cell preparations from peripheral blood after mobilization with hematopoietic growth factors have been shown to induce accelerated neutrophil and platelet recovery as compared with that induced by autologous bone marrow transplantation after myeloablative chemotherapy. Because these mononuclear cell products contain many immunocompetent cells other than hematopoietic progenitors, these accessory cells might contribute to the rapid immunohematopoietic reconstitution. We have monitored the concentrations of soluble CD4 (sCD4), sCD8, and sCD25; the recovery of the lymphocyte subsets and of natural killer (NK) cells; and the endogenous levels of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), IL-6, and granulocyte-macrophage-CSF (GM-CSF) in 12 patients who underwent high- dose chemotherapy supported by blood stem cells that were obtained by mobilization with chemotherapy and GM-CSF. The concentrations of both G- CSF and IL-6 peaked at 7 days after reinfusion of stem cells, and this transient elevation preceded the increase in the white blood cell count by approximately 5 to 7 days. The levels of sCD4 and sCD8 increased to a maximum on day 21, and the time to peak levels coincided with the maximum increase in white blood cell count, absolute neutrophil count, or lymphocytes. The levels of sCD25 were found to be elevated from day 7 to day 21. Statistically, the increases in sCD4, sCD8, sCD25, G-CSF, and IL-6 were highly significant, whereas there were no significant changes in IL-3 and GM-CSF. A rapid recovery of the NK activity was found in all 8 of the patients who could be monitored for this assay. Therefore, our study suggests that recovery of CD4+ cells, CD8+ cells, and NK activity coincided with that of neutrophils, which is preceded by a marked, but transient, elevation of IL-6 and G-CSF.

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Zinc ameliorates lead toxicity by reducing body Pb burden and restoring Pb-induced haematological and biochemical derangements

Toxicology Research and Application ◽

10.1177/2397847320956562 ◽

2020 ◽

Vol 4 ◽

pp. 239784732095656

Author(s):

Emmanuel Ike Ugwuja ◽

Nweze Vincent ◽

Ikechukwu C Ikaraoha ◽

Samuel R Ohayi

Keyword(s):

Blood Cell ◽

Cell Count ◽

Haemoglobin Concentration ◽

Lead Toxicity ◽

Oral Route ◽

Albino Rats ◽

Blood Cell Count ◽

Corpuscular Haemoglobin ◽

Mean Corpuscular Haemoglobin ◽

Biochemical Analyses

Background: Studies on nutritional factors, including zinc in ameliorating the deleterious effects of potentially toxic elements have been scarce and the findings have been inconsistent. Aim: The aim of the present study was to evaluate the ameliorative potential of zinc against lead-induced toxicity in rats. Materials and methods: Male albino rats (n = 24) assigned into four groups of six/group: normal control (NC), zinc control (ZnC; 20 mg/kg ZnCl2), lead control (PbC; 50 mg/kg PbCl2) and lead plus zinc (Pb + Zn; 50 mg/kg PbCl2 plus 20 mg/kg ZnCl2), respectively were investigated. All administrations were through oral route and lasted for 42 days after which blood samples were collected for haematological and biochemical analyses using standard techniques. Results: Results showed that packed cell volume (PCV), haemoglobin concentration (HBC), red blood cell count (RBC) were significant (p < 0.05) reduced while total white blood cell count (TWBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and platelets were significantly elevated in PbC group in comparison with NC and ZnC. Also liver and renal function parameters as well as the liver and kidney malondialdehyde (MDA) were elevated while antioxidant enzymes; catalase (CAT) and superoxide dismutase (SOD) were significantly (p < 0.05) reduced in PbC group in comparison with NC and ZnC. Concentrations of lead were in the order: blood > liver > kidney in the PbC group. In addition to restoration of the altered parameters, administration of zinc in Pb + Zn group significantly reduced the raised lead concentrations in the plasma and organs. Conclusion: Reduction in body Pb burden and restoration of Pb-induced derangements in haematological and biochemical parameters by Zn strongly support the ameliorative property of Zn against Pb-induced toxicity.

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Blood cell count and morphology, and vitamin B12 concentration in pre- and post-weaned calves

Veterinární Medicína ◽

10.17221/12/2021-vetmed ◽

2021 ◽

Vol 66 (No. 12) ◽

pp. 513-519

Author(s):

EG Katsogiannou ◽

PD Katsoulos ◽

C Ziogas ◽

MC Naskou ◽

G Christodoulopoulos ◽

...

Keyword(s):

Blood Cell ◽

Vitamin B12 ◽

Cell Count ◽

Total Population ◽

Complete Blood Count ◽

Haemoglobin Concentration ◽

Strong Positive Correlation ◽

Blood Cell Count ◽

Veal Calves ◽

Blood Cell Morphology

Haematological indicators may resent physiological variation by age. Vitamin B12 promotes haematopoiesis. The aims of this study were: 1) to compare the values of the haematological variables and the concentration of vitamin B12 in pre- or post-weaned veal calves and 2) to identify the possible association between the values of the haematological variables and the concentration of B12 in the blood of veal calves. Blood was collected on the same day from 31 pre-weaned and 31 weaned calves of the Limousine breed from the same farm. The complete blood count, including the blood cell morphology evaluation, was performed and the serum B12, total protein and albumin concentrations were determined. The serum concentration of vitamin B12, the haematocrit (HCT), the haemoglobin concentration (HGB), the platelet count and the lymphocyte count were significantly higher in the weaned calves. A very strong positive correlation was found between the concentration of the vitamin B12 and HCT and HGB before weaning, while these correlations were moderately positive following weaning and in the total population tested as well. The observed variation in the blood cell count and morphology, such as poikilocytosis and the presence of macrocytes and hypersegmented neutrophils, along with the age of the animal seem to be related to the vitamin B12 concentration.

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