RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of the candidate and address[in block letters] / Dr Rajeshwari Patil
Dept of Biochemistry,
M.R Medical College
Gulbarga-585105
2. / Name of the Institution / Mahadevappa rampure medical college
3. / Course of Study and subject / M.D. [Biochemistry]
4. / Date of Admission of Course / 30-07-2013
5. / Title of the topic
/ “THYROID PROFILE AND SERUM BUTYRYLCHOLINESTERASE IN PRE-ECLAMPSIA”
6. / Brief Resume of the Intended work
6.1. Need for the Study: / Pregnancy – induced hypertension continues to be a major obstetric problem in present day healthcare practice. It presents a great medical dilemma because it affects not only maternal health but also puts fetal development at risk. Worldwide, the hypertensive disorders of pregnancy are common and are responsible for 12% of maternal mortality during pregnancy and puerperium. Preeclampsia is the leading cause of maternal mortality in developed countries and is associated with fivefold increase in perinatal mortality. The major cause of fetal compromise in preeclampsia is reduced uteroplacental perfusion1,2. Pregnancy is usually associated with mild hyperthyroxinemia but preeclamptic women have a high incidence of hypothyroidism that might correlate with the severity of preeclampsia3,4,5. Dyslipidemia is common in preeclampsia and via oxidation of susceptible lipids, may contribute to endothelial activation. Hyperlipidemia in preeclampsia is associated with predominance of both atherogenic small low-density lipoproteins(LDL) and vascular cell adhesion molecules6,7.
Butyrylcholinesterase is a serum esterase which primarily synthesized in liver and released into plasma immediately following its synthesis. Increased butyrylcholinesterase activity is found to be associated with altered lipid metabolism such as hyperlipoproteinemia, obesity & diabetes. Hence the current study is designed to know the association between thyroid profile and butyrylcholinesterase in patients with pre-eclampsia.
6.2. Review of Literature: / Pre-eclampsia is a leading cause of maternal and fetal/neonatal morbidity and mortality worldwide. Pre-eclampsia is a multi-system disorder of pregnancy, which is characterized by hypertension [Blood pressure > 140/90 mmHg] with proteinuria [urinary protein excretion of >300mg/l in 24hour specimen] after 20 weeks of gestation in previously normotensive non-proteinuric pregnant women8,9. Between 5% and 15% of pregnant women experience thyroid abnormalities, a fact which justifies screening by means of clinical laboratory testing10. There is a high incidence of thyroid dysfunction during pregnancy resulting in adverse maternal [miscarriages, anaemia in pregnancy, pre-eclampsia, abruptio placenta and post-partum haemorrhage] and fetal effects [premature birth, low birth weight, increased neonatal respiratory distress] which may justify screening for thyroid function during pregnancy11. Mothers who had early-onset pre-eclampsia, were of significantly lower birth weight12. Maternal thyroid dysfunction during pregnancy has been shown to be associated with a number of adverse outcomes. For example, elevated maternal thyroid-stimulating hormone [TSH] has been associated with an increased risk of pre-term birth, placental abruption, fetal death and impaired neurological development in the child13,14.
Butyrylcholinesterase is a serum esterase which primarily synthesized in liver15 and released into plasma immediately following its synthesis. This enzyme is also found in the small intestine, smooth muscle, adipose tissue, brain and other tissues, but it is not known whether this enzyme originates only from blood, or whether it can be synthesized in those tissues as well. The true physiological function of butyrylcholinesterase has not yet been identified. It was suggested that it is precursor of acetylcholinesterase in the nervous system, with an important role in the regulation of slow impulse conduction in the nervous system and that is included in the hydrolysis of ingested esters from plant sources16,17. A decrease in butyrylcholinesterase activity in plasma is an indicator of pesticide poisoning. Results of some investigators have shown that butyrylcholinesterase is probably involved in lipid metabolism. Clitherow et al suggested that butyrylcholinesterase might hydrolyse butyrylcholine possibly formed during fatty acid metabolism18. Ballantyne et al showed that butyrylcholinesterase occurred in the sebaceous gland and adipose tissue and suggested that butyrylcholinesterase took part in lipid metabolism19,20.An increased serum butyrylcholinesterase activity is usually observed in conditions associated with altered lipid metabolism such as hyperlipoproteinemia, obesity and diabetes21-26. Thus increased activity of butyrylcholinesterase was found when triglyceride [TG], very low density lipoprotein [VLDL] or low density lipoprotein [LDL] concentrations were increased in animal model of diabetic & obesity27,28.
Pre-eclampsia and related disorders are known to affect function of various organs involved in lipid and lipoprotein metabolism. Several studies have shown that endothelial dysfunction is related to hyperlipidemia29,30. Significantly elevated plasma concentration of Triglycerides [TG], phospolipids and total lipids and decreased high density lipoprotein – cholesterol [ HDL-C ] concentrations were found in women with pre-eclampsia in comparison to normal pregnancy31,32. In pre-eclampsia there is failure of estrogen production due to placental dysfunction resulting in lowering of Thyroxine Binding Globulin [TBG], Total T3, Total T4 along with growth retardation of fetus33. Apart from maintaining friendly lipid profile, estrogen changes the vascular tone by increasing nitrous oxide production. It stabilizes the endothelial cells, enhances antioxidant effects and alters fibrinolytic protein34. All these are cardio protective mechanisms, which could be dearranged in pre-eclampsia.
6.3. Objective of the study: / 1. To estimate Serum T3, T4, TSH , lipid profile and Serum Butyrylcholinesterase levels in patients with Pre-eclampsia
2. To correlate Serum T3, T4 and TSH with lipid profile &
Serum Butyrylcholinesterase in Pre-eclampsia
7. / Material and methods
7.1 Source of Data: / The study would be undertaken at Basaveshwar Teaching and General Hospital attached to M.R.Medical College, Gulbarga.
Present study will comprise of 50 normal pregnant women and 50 cases of Pre-eclampsia admitted in wards of department of OBG. Duration period of the study: 2 years Nov 2013 to Oct 2015.
7.2 Methods of collection data: [including sampling procedure if any] / Under aseptic conditions 5 ml of venous blood samples will be drawn into plain vacutainers from ante-cubital vein. The collected blood will be allowed to clot for 30 minutes, and then centrifuged at 2000 g for 15 minutes for clear separation of serum. All assays will be performed immediately after serum gets separated. Serum butyrylcholinesterase will be determined on semiautomatic biochemical analyzer using commercial kit. Concentrations of serum TC, TG, LDL-c, HDL-c, were determined on fully automatic biochemistry analyzer (Roche C-111) using enzymatic colorimetric kits (Roche diagnostic kits).
Inclusion Criteria: / The pre-eclamptic patients diagnosed by presence of persistent hypertension more than 140/90mmHg
Exclusion Criteria: / Women having history of multiple fetuses, Chronic hypertension, Renal disease, Diabetes Mellitus and addictions like Smoking and Alcoholism and other pre-existing Medical conditions will be excluded from the study
7.3 DDoes the study required any investigation intervention to be conducted on patients or other humans or animals? If so, please describe briefly. / The present study requires investigation to conduct on humans as per ethical guidelines. Volunteer written informed consent will be obtained from all the patients & controls of the study.
7.4 Has ethical clearance been obtained from your institution in case of 7.3 / Yes
8. / List of References
1. Bellany L, Casas JP, Hingorani AD and Williams DJ. Preeclampsia and risk of cardiovascular diseased cancer in later life: systematic review and meta-analysis. Br.Med.J 2007;335:974
2. Solomon CG and Seely EW. Brief review: hypertension in pregnancy: A manifestation of insulin resistance syndrome? Hypertension 2001;37: 232-239.
3. Qublan HS, Al-Kaisi IJ, Hindawi IM, Hiasat MS, Awamleh I and Hamaideh AH et al. Severe preeclampsia and maternal thyroid function. J.Obstet Gynaecol 2003;23:244-246.
4. Kaya E, Sahin Y, Ozkececi Z and Pasaoglu H. Relation between birth weight and thyroid function in preeclampsia-eclampsia.Gynaecol.Obstet.Invest 1994;37:30-33.
5. Kumar A, Ghosh BK and Murthy NS. Maternal thyroid hormonal status in preeclampsia. Indian J.Med Sci 2005;59:57-63.
6. Llurba E, Gratacos E, Martin-Gallan P, Cabero L, Dominguez C. A comprehensive study of oxidative stress and antioxidant status in preeclampsia and normal pregnancy. Free Radi.Biol.Med 2004;37(4):557-570.
7. De J, Mukhopathyay AK, and Saha PK. Study of serum lipid profile in pregnancy induced hypertension.Indian.J.Clin.Biochem 2006;21(2):165-168.
8. Cunnigham FG, Leveno KL, Bloom SL Hauth JC, Gilstrap LC and Wenstrom KD et al. Hypertensive
disorders in pregnancy. In: Cunnigham FG, Leveno KL, Bloom SL, editors. Williams Obstetrics. 22nd
ed. NewYork; McGraw-Hill; 2005: chap 34, 1237.
9. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365:785–99.
10. Glinoer D The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine adaptation from
Physiology to Pathology. Endocrine Reviews 1997; 18:404-33.
11. Lazarus JH. Screening for thyroid dysfunction in pregnancy: is it worthwhile? J Thyroid Res 2011;
2011:397012. Epub 2011 Jun 8.
12. Obed SA and Patience A. Birth Weight and Ponderal Index in Pre- Eclampsia: A Comparative Study.
Ghana Med J 2006 March; 40[1]: 8–13.
13. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ et al. Subclinical hypothyroidism
and pregnancy outcomes. Obstetrics and Gynecology 2005; 105: 239–45.
14. Allan WC, Haddow JE, Palomaki GE, Williams JR, Mitchell ML, Hermos RJ et al. Maternal thyroid
deficiency and pregnancy complications: implications for population screening. Journal of Medical
Screening 2000; 7:127–30.
15. Silver A. Pseudocholinesterases. In: The biology of cholinesterases. North-Holland Publishing
Company, Amsterdam. 1974; p 411–449.
16. Hoffmanwe, Wilson BW, Solter P F. Cholinesterases. In: Loeb W F, Quimby F W [ed] The clinical
chemistry of laboratory animals, 2nd ed. Taylor & Francis, Philadelphia. 1999; p 430 – 440.
17. Kutty K M .Biological function of cholinesterase. Clin Biochem. 1980; 13[6]: 239–243.
18. Clitherow JW, Mitchard M, Harper NJ. The possible biological function of pseudocholinesterase. Nature 1963; 199:1000–1001.
19. Ballantyne B. Histochemical and biochemical aspects of cholinesterase activity of adipose tissue. Arch Int Pharmacodyn1968; 173[2]: 343–349.
20. Ballantyne B, Bunch GA. Esterase histochemistry in sebaceous glands. Dermatologica1967; 134: 51–59.
21. Annapurna V, Senciall I, Davis AJ, Kutty KM. Relationship between serum pseudocholinesterase and triglycerides in experimentally induced diabetes mellitus in rats. Diabetologia1991; 34: 320–324.
22. Kutty K M, Huang S N, Kean K T. Pseudocholinesterase in obesity: Hypercaloric diet induced changes in experimental obese mice. Experientia1981; 37: 1141–1142.
23. Kutty KM, Payne RH. Serum pseudocholinesterase and very-low-density lipoprotein metabolism. J Clin Lab Anal 1994; 8: 247– 250.
24. Kean K T, Kutty K M, Huang S N, Jain R. A study of pseudocholinesterase induction in experimental obesity. J Am Coll Nutr 1986; 5: 253–261.
25. Abbott C A, Mackness MI, Kumar S, Olukoga AO, Gordon C, Arrol S, Bhatnagar D, Boulton AJM, Durrington P N. Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus. Clinical Science1993; 85: 77–81.
26. Rustemeijer C, Schouten J A, Voerman H J, Beynen A C, Donker A J M, Heine R J. Is pseudocholinesterase activity related to markers of triacylglycerol synthesis in type II diabetes mellitus? Clinical Science2001; 101: 29–35.
27. Cucuianu M, Popescu T A, Haragus S T. Pseudocholinesterase in obese and hyperlipemic subjects. Clin Chim Acta 1968; 22: 151–155.
28. Cucuianu M, Popescu T A, Opincaru A, Haragus S. Serum pseudocholinesterase and ceruloplasmin in various types of hyperlipoproteinemia. Clin Chim Acta 1975; 59: 19–27.
29. Chu M I, Fontaine P, Kutty K M, Murphy D, Redheendran R. Cholinesterase in serum and low density lipoprotein of hyperlipidemic patients. Clinica Chimica Acta1978; 85: 55–59.
30. Riza M, Ali Benian KG. European Journal of Obstetrics and Gynecology and Reproductive biology . Aug 1999; 85 [2]: 205-208.
31. Kokia E, Barkai G, Reichman B et al. Maternal serum lipid profile in pregnancies complicated by hypertensive disorders. Journal of Perinatal Medicine 1990; 18:473-478.
32. Sattar N, Clark KP, Green IA, et al Lipoprotein [a] levels in normal pregnancy and in pregnancy complicated with preeclampsia. Atherosclerosis 2000; 148 [2]: 407-411.
33. Banaczek Z, Wojeicka-Jagodzinska J. Concentration of lipids and lipoprotein in serum of women with pregnancy induced hypertension. Ginekologia Polska 1995 ; 66 [2]: 72-75.
34. Taddec S, Virdis A, Ghiadoni L, Mattec P, Sudano I, Bermini G. Menopause is associated with endothelial dysfunction in women. Hypertension 28: 1996; 576-582.
9. / Signature of the Candidate
10. / Remarks of the Guide / Preeclampsia is one of the leading cause of maternal and fetal morbidity and mortality. It has been established that in preeclampsia there is failure of estrogen production which intern results in the dysfunction of thyroxine binding globulin, T3 & T4, causing hypothyroidism. Several studies have shown that endothelial dysfunction leading to dyslipidemia in patients with preeclampsia. Butyrylcholinesterase is a serum esterase which is synthesized primarily in the liver, increased serum butyrylcholinesterase activity is found to be associated with altered lipid metabolism such as hyperlipoproteinemia, obesity and diabetes. Hence from this study we will be able to understand the role of butyrylcholinesterase in the pathophysiology of preeclampsia.
11. / Name and Designation
of [in block letters]
11.1. Guide / DR.SHARANABASAPPA. M. AWANTI
PROFESSOR AND HEAD
DEPARTMENT OF BIOCHEMISTRY
11.2. Signature
11.3. Co-Guide / DR.SUMAN UMESHCHANDRA
PROFESSOR
DEPARTMENT OF OBG
11.4. Signature
11.5. Head of the Department / DR.SHARANABASAPPA. M. AWANTI
11.6. Signature
12. / 12.1. Remarks of the Chairman
and Principal
12.2. Signature