Description
ABSTRACT
This study investigested the Effect of Amino Acids Phenylalanine and Glycine on Chloramphenicol CAP bonemarrow toxicity in albino Rats infected with Klebsiella pneumoniae. Twenty four rats infected with Klebsiella pneumoniae were divided into 6 groups of 4 rats each ,comprising of 4 test and 2 control groups. They were treated with : group 1 CAP alone ,group 2 CAP/ phenylalanine, group 3 CAP/glycine, group 4 CAP/phenyl/glycine Control groups: 5 N.saline , 6 not treated. The study was carried out for 21 days in which haematological and histopathological changes were monitored in the infected animals. After 7 days of treatment there was decrease in haematological parameters Pcv,Hb, Reticulocyte count and Reticulocyte index,indicating the animals were anaemic. The decrease was significant plt; 0.05 in the groups. The ability of the treatment to control infection of Klebsiella pneumonia was investigated There was no significant increase pgt;0.05 in WBC count of all the test groups, with CAP/Glycine combination being the most remarkable. The WBC differential count showed that there was significant plt;0.05 lymphocytosis with subsequent neutropenia in group 1 and 4, also blood picture report confirmed hypochromic RBC and thrombocytopenia in the two groups. After 21 days, there was significant plt;0.05 reduction in anaemia in group 2 ,3 and control groups. The presence of bone marrow aspiration count of severe erythriod hypolasia and myeloid hypoplasia in the study confirmed the decreased erythroid activity, bone marrow suppression and peripherial pancytopenia a feature of aplastic anaemia that persisted in CAP alone group. The same features except very significant erythriod hyperplasia was equally confirmed in group 4.Histopathological analysis, confirmed hypocellularity in group 1, fairly normocellularity in group 2 , clotted bone marrow to commence repair to fairly normocellularity in group 3 ,and degenerative/ necrotic changes in group 4. Finally, results obtained from this study showed that single amino acids Phenylalanine or Glycine combination with CAP protected the bone marrow and prevented anaemia bone marrow suppression and aplastic anaemia. In conclusion, single amino acid combination with CAP have obvious protective effect and decreased the bone marrow toxicity effect of CAP rather than the combination of two amino acids with CAP . In addition all the amino acids combinations enhanced the antibacterial effect of CAP.
TABLE OF CONTENT PAGES
TITTLE PAGE
CERTIFICATION ii
APPROVAL PAGE
DEDICATION iii
ACKNOWLEDGEMENT iv
TABLE OF CONTENT v
LIST OF TABLES /FIGURES vi
ABSTRACTS vii
CHAPTER ONE
1.0 INTRODUCTION
1.01 : ORIGIN 1
1.02 : SPECTRUM OF ACTIVITY 1
1.03: MECHANISM OF ACTION 2
1.04: PHARMACOKINETICS 2
1.05: RESISTANCE 2
1.06: THERAPUETIC INDICATION 3
1.07: CONTRA INDICATION 3
1.08: DRUG INTERACTION 5
1.09: ADVERSE EFFECTS
1.10: STATEMENT OF PROBLEM 9
1.11: JUSTIFICATION OF STUDY 9
1.12 : AIM AND OBJECTIVES OF STUDY 10
CHAPTER TWO
2.0 : LITERATURE REVIEW 11
2.01 : STUDIES THAT CONFIRMS CHLORAMPHENICOL HEAMATOLOGICAL TOXICITY
2.02 : STUDIES ON POSSIBLE THETAPEUTIC MANUEVERS AIMED TO AMELIORATE CHLORAMPHENICOL HEAMATOLOGICAL TOXICITY
2.03 : PHENYLALANINE 18
2.04: PROTECTIVE EFFECT OF PHENYLALANINE 20
2.05: INHIBITORY EFFECT OF PHENYLALANINE 22
2.0 6: GLYCINE 24
2.07: PROTECTIVE EFFECT OF GLYCINE 26
2.08: INHIBITORY EFFECT OF GLYCINE 28
2.09 : CLINICAL IMPORTANCE OF HEAMATOLOGICAL INDICES EMPLOYED IN THE . RESEARCH 30
CHAPTER THREE
3.0: MATERIALS AND METHODS 32
3.01: CHEMICAL/ DRUGS 32
3.02: INSTRUMENTS 32
3.03: ANIMALS
3.04 : INDUCTION OF INFECTION OF KLEBSIELLA PNEUMONIAE 33
3.05: ADMINISTRATION OF DRUGS AND AMINO ACID 33
3.06: COLLECTION OF BLOOD SAMPLES 33
3.07: HEAMATOLOGICAL ANALYSIS 34
3.08: HEAMATOLOGICAL EXAMINATION OF BONE MARROW 37
3.09: HISTOPATHOLOGICAL EXAMINATION OF BONEMARROW 38
3.10: ANIMAL OBSERVATION 39
3.11: STATISTICAL ANALYSIS 39
CHAPTER
4.0 : RESULTS
4.01: HEAMATOLOGICAL BONE MARROW ASPIRATION RESULTS
4.02 : HISTOPATHOLOGICAL RESULTS
4.03: EVALUATION OF THE EFFECTS OF VARIOUS TREATMENTS AND THEIR POTENCY ON DEVELOPMENT OF ANAEMIA CAUSED BY CAP
4.04: EVALUATION OF THE EFFECTS OF VARIOUS TREATMENTS AND THEIR POTENCY ON DEVELOPMENT OF INFECTION CAUSED BY Klebsiella pneumonia
CHAPTER 5 58
5.0 : DISCUSSION 58
5.01: CONCLUSION 61
5.02: REFERENCES 62
5.03: APPENDIX I 68
5.04 APPENDIX II 71
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