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Sub-chronic Effect Of Co-administration Of Methformine And Amilodipine On Some Haematological Indices In Experimental Animal
[A CASE STUDY OF WISTAR RATS]
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2.10 Comparative haematology of rat and human
Blood picture
In comparison to human erythrocyte counts rat erythrocyte count tend to be high due to the high metabolic rate in rat, typically in the range 6.8 – 10.05 × 106 cells/ μL while humans have red blood cell count of 4.5-5.9 × 106 cells/ μL. Hemoglobin values vary with strain and are determined based on sex, age and health. Diameter of red blood cell in rat varies between 5.7 and 7μm, depending on its maturity (Feldman et al., 2010). Mean corpuscular haemoglobin values (typically of 16 – 21pg) reflect the small size of red cells where as for human the mean corpuscular haemoglobin is typically 27-33pg. For the mean corpuscular haemoglobin concentration tends to be close to 33.5g/dL in fresh samples for human. There is a great variation in total leukocyte count and differential distribution due to the excitable nature of the animals, the site of sampling and normal diurnal variations. Lymphocytes constitute the majority white cell population in peripheral blood and are seen as a relatively homogeneous population in a healthy subject. Both large and small lymphocytes are present, the red blood cell approximating to the size of normal neutrophils and sometimes containing large, dark – staining azurophilic granules. The nuclei of the neutrophil are slightly larger than erythrocytes (Clifford and Alfred, 2011).
Neutrophils of Rat white blood cells are the next most numerous which is the opposite case in humans in which the neutrophil count has the highest count in apparently healthy individual. In comparison with human neutrophil of apparently healthy individual, Rat neutrophil shows Nuclear lobulation distribution of a slight right shift. Rat neutrophils are approximately 11μm in diameter and have pale cytoplasm with fine, diffuse granules. The nucleus is highly segmented, coiled, or ribbon - like, and has numerous indentations (Car and Eng, 2001). The formation of lobes in the granulocytes of rats (and other rodents) is preceded by the development of an annular nucleus. This is first seen in the promyelocyte stage in bone marrow, metamyelocytes appearing uniformly “doughnut-shapedâ€. In some cases the ring structure may not be entirely lost with some neutrophil cells possessing nuclei in figure of eight conformation (Clifford and Alfred, 2011). Normally monocytes are present in low numbers in peripheral blood of healthy animals, but can constitute up to 1-6% of the differential leucocyte count where as in humans monocyte also vary from 2-6% which is similar to that of the Rat. Monocytes have pleomorphic nuclei that may be round, indented, or lobular. The cytoplasm is extensive, stains pale gray blue, and often contains vacuoles. Occasionally azurophilic granules are present in the cytoplasm (Fredrickson and Harris, 2000).
Eosinophils are also normally present only in low numbers in peripheral blood in healthy animals, about 1-4% of differential leucocyte count. They are generally larger than neutrophils also with fewer segments than neutrophil, with small, round, strongly acidophilic granules which fill the cytoplasm. Basophils are uncommon, or absent, in rat blood preparations in some strains as compared to humans in which basophil differential count range from 1-2%. Large unstained cells (LUCs) constitute around 5% of a normal population of circulating white blood cells, and reflect the same situation as in other species, i.e. increases are due to reactive, activated or atypical lymphocytes, or mononuclear cells. Platelet numbers vary greatly (Hogan et al., 2002), but are greater in number with smaller individual volume than human platelets. Platelet counts, volume estimations and population statistics may be compromised by degranulation, clumping of platelets and/or partial clotting of the sample. Platelet count validity must be considered very carefully in the using microscopic examination of the blood smear since platelet count in rat is usually very high (900-1600x109/L) as compared to human with a platelet count of 150-400x109/L (Clifford and Alfred, 2011).
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ABSRACT - [ Total Page(s): 1 ]ABSTRACTMetformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 (American Diabetes Association, 2009) whereas Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP (Blood pressure). the aim is to know the effect of co-administration of this two drugs in Wistar rats ... Continue reading---
APPENDIX A - [ Total Page(s): 1 ]APPENDIXAPPENDIX 1: MATERIAL USED1% Ammonium oxalate10% Formalin salineAbsorbent paperAutomatic pipetteBrilliant cresyl blueCounting chamber Cyanmethaemoglobin standardDrabkin’s ReagentEDTA sample containerHematoxylin and Eosin stainKhan tubes/rackLeisfhmann stainLight microscopeMicrohaematocrit centrifugeNormal salinePasteur pipettePipette tipsRotary microtomeSpectrophotometerTimer Turk’s solution Universal sample bottle ... Continue reading---
APPENDIX B - [ Total Page(s): 1 ]APPENDIX IITable 1: haematological parameters in control, Metformine treated and Amilodipine treated Rats (Values are expressed as mean ± Standard error of means) Group A(1): control (untreated), Group B(2): co-administration of Metformin 0.00264/ml/132g and Amlodipine 0.000849/ml/132g at a single dose for 30 daysPARAMETERS GROUP A GROUP BPacked cell volume (%) 44.16±2.83 38.47±3.53Red blood cell count (x1012/L) 7 ... Continue reading---
LIST OF TABLES - [ Total Page(s): 1 ]LIST OF TABLESTable 1: Haematological parameters in control, Co-administration of Metformin and Amlodipine treated ... Continue reading---
LIST OF FIGURES - [ Total Page(s): 1 ]LIST OF FIGURESFigure 1: Shows mechanism of action of metformin Figure 2: Shows Pie chat representation of Packed cell volume of control, Co-administration of metformin and amlodipine treated Wistar Rats Figure 3: Shows Histogram representation of Hemoglobin and red blood cell count of control, Co-administration of metformin and amlodipine treated Wistar Rats Figure 4: Shows Histogram representation of red cell indicies of control, Co-administration of metformin and amlodipine t ... Continue reading---
TABLE OF CONTENTS - [ Total Page(s): 1 ]TABLE OF CONTENTTitle page Declaration Certification Dedication Acknowledgement Table of content List of table List of figures Abstract CHAPTER ONE1.0 Introduction 1.1 Background of study 1.2 Statement of Problems 1.3 Justifications 1.4 Aims 1.5 Research Objectives 1.6 Research Hypothesis 1.7 Significance of research CHAPTER TWO2.0 Literature review 2.1 Metformin 2.1.1 ... Continue reading---
CHAPTER ONE - [ Total Page(s): 2 ]CHAPTER ONE1.0 INTRODUCTION1.1 Background of the studyMetformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 (American Diabetes Association, 2009). Currently, many clinical practice guidelines for patients with type 2 diabetes, including the American Diabetes Association (ADA), the European Association for the Study of Diabetes ... Continue reading---
CHAPTER THREE - [ Total Page(s): 4 ]From the above table,Km of rats= 6 Km of human= 37For Amlodipine, Human dose= 10mg/70kg 1kg=10/70 =0.14mg/kgAED of Amilodipine= 0.14×(6/37) =0.02mg/kgAverage weight of experimental Animal is 132g(0.132kg)If 0.02mg of Amlodipine is administered per kg.bw,(0.02×0.132)mg of Amlodipine was administered to ... Continue reading---
CHAPTER FOUR - [ Total Page(s): 6 ]CHAPTER FOUR4.0 Results4.1 Hematological parameter in control and test groups As summarized in table 1, the mean RBC counts were 7.62 ± 2.83 x1012/L for the control and 6.53 ± 0.57 x1012/L for co-administration of metformin and amlodipine fed groups respectively. Although, decrease in RBC counts was observed in the treated (co-administration of metformin and amlodipine) dose group, these were statistically significant compared to control groups (student t test P0.05) higher in the tr ... Continue reading---
CHAPTER FIVE - [ Total Page(s): 2 ]CHAPTER FIVE5.0 DiscussionMetformin (1,1-dimethylbiguanide) is the most widely used drug to treat type 2 diabetes, and is one of only two oral anti-diabetic drugs on the World Health Organization (WHO) list of essential medicines (American Diabetes Association, 2009). Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP. Co-administration of Metformin and Amlodipine have been discovered to lead to vitamin B12 deficiency. Al ... Continue reading---
REFRENCES - [ Total Page(s): 4 ]Senol, M.G., Sonmez, G., Ozdag, F. and Saracoglu, M. (2008). Reversible myelopathy with vitamin B12 deficiency. Singapore Medical Journal. 49(11): 330-332.Srinivasan, S., Ambler, G.R., Baur, L.A., Garnett, S.P. and Tepsa, M. (2006). Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. Journal of Clinical Endocrinology and Metabolism. 91: 2074-2080. Sterne, J. (1957). Du nouveau dans les anti ... Continue reading---
